Systems ~ Variants of Uncertain Significance
~ Genetics of Breast & Ovarian Cancer

Systems, methods, models, algorithms, assays, consortia for assessing/classifying variants of uncertain significance

List was last updated on Oct 6, 2019 @ 1:37 pm.


    • A global functional analysis of missense mutations reveals two major hotspots in the PALB2 tumor suppressor.
    • Rodrigue A, Margaillan G, Torres Gomes T, Coulombe Y, Montalban G, da Costa E Silva Carvalho S, Milano L, Ducy M, De-Gregoriis G, Dellaire G, Araújo da Silva W Jr, Monteiro AN, Carvalho MA, Simard J, Masson JY.
    • Nucleic Acids Res. 2019 Oct 5. pii: gkz780. doi: 10.1093/nar/gkz780. [Epub ahead of print]
    • Adding RNA-Seq, Ambry Genetics Expects to Reduce VUS Results in Hereditary Cancer Tests.
    • [No author given]
    • GenomeWeb. 2019 Oct 4.
    • News
    • A Functional Analysis of the Unclassified Pro2767Ser BRCA2 Variant Reveals Its Potential Pathogenicity that Acts by Hampering DNA Binding and Homology-Mediated DNA Repair.
    • Esposito MV, Minopoli G, Esposito L, D'Argenio V, Di Maggio F, Sasso E, D'Aiuto M, Zambrano N, Salvatore F.
    • Cancers (Basel). 2019 Sep 28;11(10). pii: E1454. doi: 10.3390/cancers11101454.
    • Novel Genetic Markers for Early Detection of Elevated Breast Cancer Risk in Women.
    • Wu B, Peng Y, Eggert J, Alexov E.
    • Int J Mol Sci. 2019 Sep 28;20(19). pii: E4828. doi: 10.3390/ijms20194828.
    • A CRISPR-based base-editing screen for the functional assessment of BRCA1 variants.
    • Kweon J, Jang AH, Shin HR, See JE, Lee W, Lee JW, Chang S, Kim K, Kim Y.
    • Oncogene. 2019 Aug 29. doi: 10.1038/s41388-019-0968-2. [Epub ahead of print]
    • A novel BRCA1 germline mutation promotes triple-negative breast cancer cells progression and enhances sensitivity to DNA damage agents.
    • Xu K, Shi Y, Wang X, Chen Y, Tang L, Guan X.
    • Cancer Genet. 2019 Aug 23;239:26-32. doi: 10.1016/j.cancergen.2019.08.004. [Epub ahead of print]
    • Functional analysis of clinical BARD1 germline variants.
    • Toh MR, Chong ST, Chan SH, Low CE, Ishak NDB, Lim JQ, Courtney E, Ngeow J.
    • Cold Spring Harb Mol Case Stud. 2019 Aug 1;5(4). pii: a004093. doi: 10.1101/mcs.a004093. Print 2019 Aug.
    • Incorporation of semi-quantitative analysis of splicing alterations for the clinical interpretation of variants in BRCA1 and BRCA2 genes.
    • Montalban G, Bonache S, Moles-Fernández A, Gadea N, Tenés A, Torres-Esquius S, Carrasco E, Balmaña J, Diez O, Gutiérrez-Enríquez S.
    • Hum Mutat. 2019 Jul 25. doi: 10.1002/humu.23882. [Epub ahead of print]
    • Targeted RNA-seq successfully identifies normal and pathogenic splicing events in breast/ovarian cancer susceptibility and Lynch syndrome genes.
    • Brandão RD, Mensaert K, López-Perolio I, Tserpelis D, Xenakis M, Lattimore V, Walker LC, Kvist A, Vega A, Gutiérrez-Enríquez S, Díez O; KConFaB Investigators, de la Hoya M, Spurdle AB, De Meyer T, Blok MJ.
    • Int J Cancer. 2019 Jul 15;145(2):401-414. doi: 10.1002/ijc.32114. Epub 2019 Feb 7.
    • Assessment of blind predictions of the clinical significance of BRCA1 and BRCA2 variants.
    • Cline MS, Babbi G, Bonache S, Cao Y, Casadio R, de la Cruz X, Díez O, Gutiérrez-Enríquez S, Katsonis P, Lai C, Lichtarge O, Martelli PL, Mishne G, Moles-Fernández A, Montalban G, Mooney SD, O'Conner R, Ootes L, Özkan S, Padilla N, Pagel KA, Pejaver V, Radivojac P, Riera C, Savojardo C, Shen Y, Sun Y, Topper S, Parsons MT, Spurdle AB, Goldgar DE; ENIGMA Consortium.
    • Hum Mutat. 2019 Jul 11. doi: 10.1002/humu.23861. [Epub ahead of print]
    • Functional coding and non-coding variants in human BRCA1 gene and their use in genetic screening.
    • Tuncel G, Ergören MÇ.
    • Med Oncol. 2019 Jul 3;36(8):71. doi: 10.1007/s12032-019-1294-9.
    • Review
    • Assessing the performance of in-silico methods for predicting the pathogenicity of variants in the gene CHEK2, among Hispanic females with breast cancer.
    • Voskanian A, Katsonis P, Lichtarge O, Pejaver V, Radivojac P, Mooney SD, Capriotti E, Bromberg Y, Wang Y, Miller M, Martelli PL, Savojardo C, Babbi G, Casadio R, Cao Y, Sun Y, Shen Y, Garg A, Pal D, Yu Y, Huff CD, Tavtigian SV, Young E, Neuhausen SL, Ziv E, Pal LR, Andreoletti G, Brenner S, Kann M.
    • Hum Mutat. 2019 Jun 26. doi: 10.1002/humu.23849. [Epub ahead of print]
    • Discovery of a pathogenic variant rs139379666 (p. P2974L) in ATM for breast cancer risk in Chinese populations.
    • Guo X, Lin W, Bai M, Li H, Wen W, Zeng C, Chen Z, He J, Chen J, Cai Q, Long J, Jia WH, Shu XO, Zheng W.
    • Cancer Epidemiol Biomarkers Prev. 2019 Jun 3. pii: cebp.1294.2018. doi: 10.1158/1055-9965.EPI-18-1294. [Epub ahead of print]
    • [Germline CHEK2 Gene Mutations in Hereditary Breast Cancer Predisposition - Mutation Types and their Biological and Clinical Relevance.]
    • Kleiblová P, Stolařová L, Křížová K, Lhota F, Hojný J, Zemánková P, Havránek O, Vočka M, Černá M, Lhotová K, Borecká M, Janatová M, Soukupová J, Ševčík J, Zimovjanová M, Kotlas J, Panczak A, Veselá K, Červenková J, Schneiderová M, Burócziová M, Burdová K, Stránecký V, Foretová L, Macháčková E, Tavandzis S, Kmoch S, Macůrek L, Kleibl Z.
    • Klin Onkol. 2019 Summer;32(Supplementum2):36-50. doi: 10.14735/amko2019S36.
    • Hereditary Cancer Syndromes-A Primer on Diagnosis and Management: Part 1: Breast-Ovarian Cancer Syndromes.
    • Samadder NJ, Giridhar KV, Baffy N, Riegert-Johnson D, Couch FJ.
    • Mayo Clin Proc. 2019 Jun;94(6):1084-1098. doi: 10.1016/j.mayocp.2019.02.017.
    • Predicting Pathogenicity of Missense Variants with Weakly Supervised Regression.
    • Cao Y, Sun Y, Karimi M, Chen H, Moronfoye O, Shen Y.
    • Hum Mutat. 2019 May 30. doi: 10.1002/humu.23826. [Epub ahead of print]
    • Minigene Splicing Assays Identify 12 Spliceogenic Variants of BRCA2 Exons 14 and 15.
    • Fraile-Bethencourt E, Valenzuela-Palomo A, Díez-Gómez B, Caloca MJ, Gómez-Barrero S, Velasco EA.
    • Front Genet. 2019 May 28;10:503. doi: 10.3389/fgene.2019.00503. eCollection 2019.
    • Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification.
    • Parsons MT, Tudini E, Li H, Hahnen E, Wappenschmidt B, Feliubadaló L, Aalfs CM, Agata S, Aittomäki K, Alducci E, Alonso-Cerezo MC, Arnold N, Auber B, Austin R, Azzollini J, Balmaña J, Barbieri E, Bartram CR, Blanco A, Blümcke B, Bonache S, Bonanni B, Borg Å, Bortesi B, Brunet J, Bruzzone C, Bucksch K, Cagnoli G, Caldés T, Caliebe A, Caligo MA, Calvello M, Capone GL, Caputo SM, Carnevali I, Carrasco E, Caux-Moncoutier V, Cavalli P, Cini G, Clarke EM, Concolino P, Cops EJ, Cortesi L, Couch FJ, Darder E, de la Hoya M, Dean M, Debatin I, Del Valle J, Delnatte C, Derive N, Diez O, Ditsch N, Domchek SM, Dutrannoy V, Eccles DM, Ehrencrona H, Enders U, Evans DG, Faust U, Felbor U, Feroce I, Fine M, Galvao HCR, Gambino G, Gehrig A, Gensini F, Gerdes AM, Germani A, Giesecke J, Gismondi V, Gómez C, Gómez Garcia EB, González S, Grau E, Grill S, Gross E, Guerrieri-Gonzaga A, Guillaud-Bataille M, Gutiérrez-Enríquez S, Haaf T, Hackmann K, Hansen TVO, Harris M, Hauke J, Heinrich T, Hellebrand H, Herold KN, Honisch E, Horvath J, Houdayer C, Hübbel V, Iglesias S, Izquierdo A, James PA, Janssen LAM, Jeschke U, Kaulfuß S, Keupp K, Kiechle M, Kölbl A, Krieger S, Kruse TA, Kvist A, Lalloo F, Larsen M, Lattimore VL, Lautrup C, Ledig S, Leinert E, Lewis AL, Lim J, Loeffler M, López-Fernández A, Lucci-Cordisco E, Maass N, Manoukian S, Marabelli M, Matricardi L, Meindl A, Michelli RD, Moghadasi S, Moles-Fernández A, Montagna M, Montalban G, Monteiro AN, Montes E, Mori L, Moserle L, Müller CR, Mundhenke C, Naldi N, Nathanson KL, Navarro M, Nevanlinna H, Nichols CB, Niederacher D, Nielsen HR, Ong KR, Pachter N, Palmero EI, Papi L, Pedersen IS, Peissel B, Pérez-Segura P, Pfeifer K, Pineda M, Pohl-Rescigno E, Poplawski NK, Porfirio B, Quante AS, Ramser J, Reis RM, Revillion F, Rhiem K, Riboli B, Ritter J, Rivera D, Rofes P, Rump A, Salinas M, Sánchez de Abajo AM, Schmidt G, Schoenwiese U, Seggewiß J, Solanes A, Steinemann D, Stiller M, Stoppa-Lyonnet D, Sullivan KJ, Susman R, Sutter C, Tavtigian SV, Teo SH, Teulé A, Thomassen M, Tibiletti MG, Tognazzo S, Toland AE, Tornero E, Törngren T, Torres-Esquius S, Toss A, Trainer AH, van Asperen CJ, van Mackelenbergh MT, Varesco L, Vargas-Parra G, Varon R, Vega A, Velasco Á, Vesper AS, Viel A, Vreeswijk MPG, Wagner SA, Waha A, Walker LC, Walters RJ, Wang-Gohrke S, Weber BHF, Weichert W, Wieland K, Wiesmüller L, Witzel I, Wöckel A, Woodward ER, Zachariae S, Zampiga V, Zeder-Göß C; KConFab Investigators, Lázaro C, De Nicolo A, Radice P, Engel C, Schmutzler RK, Goldgar DE, Spurdle AB.
    • Hum Mutat. 2019 May 27. doi: 10.1002/humu.23818. [Epub ahead of print]
    • Diagnostic mRNA splicing assay for variants in BRCA1 and BRCA2 identified two novel pathogenic splicing aberrations.
    • Wangensteen T, Felde CN, Ahmed D, Mæhle L, Ariansen SL.
    • Hered Cancer Clin Pract. 2019 May 22;17:14. doi: 10.1186/s13053-019-0113-9. eCollection 2019.
    • BRCA1- and BRCA2-specific in silico tools for variant interpretation in the CAGI 5 ENIGMA challenge.
    • Padilla N, Moles-Fernández A, Riera C, Montalban G, Özkan S, Ootes L, Bonache S, Díez O, Gutiérrez-Enríquez S, de la Cruz X.
    • Hum Mutat. 2019 May 21. doi: 10.1002/humu.23802. [Epub ahead of print]
    • Exploring the use of molecular dynamics in assessing protein variants for phenotypic alterations.
    • Garg A, Pal D.
    • Hum Mutat. 2019 May 20. doi: 10.1002/humu.23800. [Epub ahead of print]
    • Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers.
    • Nones K, Johnson J, Newell F, Patch AM, Thorne H, Kazakoff SH, de Luca XM, Parsons MT, Ferguson K, Reid L, Reed AEM, Srihari S, Lakis V, Davidson AL, Mukhopadhyay P, Holmes O, Xu Q, Wood S, Leonard C; Kathleen Cuningham Foundation Consortium for Research into Familial Aspects of Breast Cancer (kConFab); Australian Breast Cancer Tissue Bank (ABCTB); Brisbane Breast Bank (BBB), Beesley J, Harris J, Barnes D, Degasperi A, Ragan MA, Spurdle AB, Khanna KK, Lakhani SR, Pearson JV, Nik-Zainal S, Chenevix-Trench G, Waddell N, Simpson PT.
    • Ann Oncol. 2019 May 15. pii: mdz132. doi: 10.1093/annonc/mdz132. [Epub ahead of print]

    Editorial:

    Journey's End: the quest for BRCA-like hereditary breast cancer genes is nearly over.

    • Identification of deleterious germline CHEK2 mutations and their association with breast and ovarian cancer.
    • Kleiblova P, Stolarova L, Krizova K, Lhota F, Hojny J, Zemankova P, Havranek O, Vocka M, Cerna M, Lhotova K, Borecka M, Janatova M, Soukupova J, Sevcik J, Zimovjanova M, Kotlas J, Panczak A, Vesela K, Cervenkova J, Schneiderova M, Burocziova M, Burdova K, Stranecky V, Foretova L, Machackova E, Tavandzis S, Kmoch S, Macurek L, Kleibl Z.
    • Int J Cancer. 2019 May 3. doi: 10.1002/ijc.32385. [Epub ahead of print]
    • Functional characterization of CHEK2 variants in a Saccharomyces cerevisiae system.
    • Delimitsou A, Fostira F, Kalfakakou D, Apostolou P, Konstantopoulou I, Kroupis C, Papavassiliou AG, Kleibl Z, Stratikos E, Voutsinas GE, Yannoukakos D.
    • Hum Mutat. 2019 May;40(5):631-648. doi: 10.1002/humu.23728. Epub 2019 Mar 9.
    • A reference system for BRCA mutation detection based on next-generation sequencing in the Chinese population.
    • Qu S, Chen Q, Yi Y, Shao K, Zhang W, Wang Y, Bai J, Li X, Liu Z, Wang X, Jing R, Guan Y, Yi X, Yan M, Cao B, Chen F, Zhu S, Yang X, Wu Y, Huang J.
    • J Mol Diagn. 2019 Apr 23. pii: S1525-1578(18)30284-8. doi: 10.1016/j.jmoldx.2019.03.003. [Epub ahead of print]
    • Germline Missense Variants in BRCA1: New Trends and Challenges for Clinical Annotation.
    • Golubeva VA, Nepomuceno TC, Monteiro ANA.
    • Cancers (Basel). 2019 Apr 12;11(4). pii: E522. doi: 10.3390/cancers11040522.
    • Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation.
    • Fernandes VC, Golubeva VA, Di Pietro G, Shields C, Amankwah K, Nepomuceno TC, de Gregoriis G, Abreu RBV, Harro C, Gomes TT, Silva RF, Suarez-Kurtz G, Couch FJ, Iversen ES, Monteiro ANA, Carvalho MA.
    • J Biol Chem. 2019 Apr 12;294(15):5980-5992. doi: 10.1074/jbc.RA118.005274. Epub 2019 Feb 14.
    • Variant classification changes over time in BRCA1 and BRCA2.
    • Mighton C, Charames GS, Wang M, Zakoor KR, Wong A, Shickh S, Watkins N, Lebo MS, Bombard Y, Lerner-Ellis J.
    • Genet Med. 2019 Apr 11. doi: 10.1038/s41436-019-0493-2. [Epub ahead of print]
    • Data-adaptive multi-locus association testing in subjects with arbitrary genealogical relationships.
    • Gong G, Wang W, Hsieh CL, Van Den Berg DJ, Haiman C, Oakley-Girvan I, Whittemore AS.
    • Stat Appl Genet Mol Biol. 2019 Apr 8. pii: /j/sagmb.ahead-of-print/sagmb-2018-0030/sagmb-2018-0030.xml. doi: 10.1515/sagmb-2018-0030. [Epub ahead of print]
    • Alternative transcript imbalance underlying breast cancer susceptibility in a family carrying PALB2 c.3201+5G>T.
    • Duran-Lozano L, Montalban G, Bonache S, Moles-Fernández A, Tenés A, Castroviejo-Bermejo M, Carrasco E, López-Fernández A, Torres-Esquius S, Gadea N, Stjepanovic N, Balmaña J, Gutiérrez-Enríquez S, Diez O.
    • Breast Cancer Res Treat. 2019 Apr;174(2):543-550. doi: 10.1007/s10549-018-05094-8. Epub 2018 Dec 14.
    • Case report
    • Functional analysis of BARD1 missense variants in homology-directed repair and damage sensitivity.
    • Adamovich AI, Banerjee T, Wingo M, Duncan K, Ning J, Martins Rodrigues F, Huang KL, Lee C, Chen F, Ding L, Parvin JD.
    • PLoS Genet. 2019 Mar 29;15(3):e1008049. doi: 10.1371/journal.pgen.1008049. [Epub ahead of print]
    • Quick Uptakes: Taking the Uncertainty Out of Interpreting BRCA Variants.
    • Voelker R.
    • JAMA. 2019 Mar 20. doi: 10.1001/jama.2019.0967. [Epub ahead of print]

    Original research:

    BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2.

    • Alternative splicing and ACMG-AMP-2015-based classification of PALB2 genetic variants: an ENIGMA report.
    • Lopez-Perolio I, Leman R, Behar R, Lattimore V, Pearson JF, Castéra L, Martins A, Vaur D, Goardon N, Davy G, Garre P, García-Barberán V, Llovet P, Pérez-Segura P, Díaz-Rubio E, Caldés T, Hruska KS, Hsuan V, Wu S, Pesaran T, Karam R, Vallon-Christersson J, Borg A, Investigators K, Valenzuela-Palomo A, Velasco EA, Southey M, Vreeswijk MPG, Devilee P, Kvist A, Spurdle AB, Walker LC, Krieger S, de la Hoya M.
    • J Med Genet. 2019 Mar 19. pii: jmedgenet-2018-105834. doi: 10.1136/jmedgenet-2018-105834. [Epub ahead of print]
    • Mis-splicing in breast cancer: identification of pathogenic BRCA2 variants by systematic minigene assays.
    • Fraile-Bethencourt E, Valenzuela-Palomo A, Díez-Gómez B, Goina E, Acedo A, Buratti E, Velasco EA.
    • J Pathol. 2019 Mar 18. doi: 10.1002/path.5268. [Epub ahead of print]
    • Usefulness and Limitations of Comprehensive Characterization of mRNA Splicing Profiles in the Definition of the Clinical Relevance of BRCA1/2 Variants of Uncertain Significance.
    • Gelli E, Colombo M, Pinto AM, De Vecchi G, Foglia C, Amitrano S, Morbidoni V, Imperatore V, Manoukian S, Baldassarri M, Lo Rizzo C, Catania L, Frullanti E, Tagliafico E, Cortesi L, Spaggiari F, Mencarelli MA, Trevisson E, Radice P, Renieri A, Ariani F.
    • Cancers (Basel). 2019 Mar 1;11(3). pii: E295. doi: 10.3390/cancers11030295.
    • DNA breakpoint assay reveals a majority of gross duplications occur in tandem reducing VUS classifications in breast cancer predisposition genes.
    • Richardson ME, Chong H, Mu W, Conner BR, Hsuan V, Willett S, Lam S, Tsai P, Pesaran T, Chamberlin AC, Park MS, Gray P, Karam R, Elliott A.
    • Genet Med. 2019 Mar;21(3):683-693. doi: 10.1038/s41436-018-0092-7. Epub 2018 Jul 28.
    • BRCA1/2 Variant Data-Sharing Practices.
    • Bollinger JM, Sanka A, Dolman L, Liao RG, Cook-Deegan R.
    • J Law Med Ethics. 2019 Mar;47(1):88-96. doi: 10.1177/1073110519840487.
    • Toward automation of germline variant curation in clinical cancer genetics.
    • Ravichandran V, Shameer Z, Kemel Y, Walsh M, Cadoo K, Lipkin S, Mandelker D, Zhang L, Stadler Z, Robson M, Offit K, Vijai J.
    • Genet Med. 2019 Feb 21. doi: 10.1038/s41436-019-0463-8. [Epub ahead of print]
    • Integrative data fusion for comprehensive assessment of a novel CHEK2 variant using combined genomics, imaging, and functional-structural assessments via protein informatics.
    • Hines SL, Mohammad AN, Jackson J, Macklin S, Caulfield TR.
    • Mol Omics. 2019 Feb 11;15(1):59-66. doi: 10.1039/c8mo00137e.
    • Quantifying BRCA1 and BRCA2 mRNA Isoform Expression Levels in Single Cells.
    • Lattimore VL, Pearson JF, Morley-Bunker AE, Investigators K, Spurdle AB, Robinson BA, Currie MJ, Walker LC.
    • Int J Mol Sci. 2019 Feb 6;20(3). pii: E693. doi: 10.3390/ijms20030693.
    • The functional impact of variants of uncertain significance in BRCA2.
    • Mesman RLS, Calléja FMGR, Hendriks G, Morolli B, Misovic B, Devilee P, van Asperen CJ, Vrieling H, Vreeswijk MPG.
    • Genet Med. 2019 Feb;21(2):293-302. doi: 10.1038/s41436-018-0052-2. Epub 2018 Jul 10.
    • GFP-Fragment Reassembly Screens for the Functional Characterization of Variants of Uncertain Significance in Protein Interaction Domains of the BRCA1 and BRCA2 Genes.
    • Caleca L, Colombo M, van Overeem Hansen T, Lázaro C, Manoukian S, Parsons MT, Spurdle AB, Radice P.
    • Cancers (Basel). 2019 Jan 28;11(2). pii: E151. doi: 10.3390/cancers11020151.
    • The effects of genomic germline variant reclassification on clinical cancer care.
    • Slavin TP, Manjarrez S, Pritchard CC, Gray S, Weitzel JN.
    • Oncotarget. 2019 Jan 11;10(4):417-423. doi: 10.18632/oncotarget.26501. eCollection 2019 Jan 11.
    • Additional molecular and clinical evidence open the way to definitive IARC classification of the BRCA1 c.5332G > A (p.Asp1778Asn) variant.
    • Minucci A, Lalle M, De Leo R, Mazzuccato G, Scambia G, Urbani A, Fagotti A, Concolino P, Capoluongo E.
    • Clin Biochem. 2019 Jan;63:54-58. doi: 10.1016/j.clinbiochem.2018.10.004. Epub 2018 Oct 10.
    • Comprehensive annotation of BRCA1 and BRCA2 missense variants by functionally validated sequence-based computational prediction models.
    • Hart SN, Hoskin T, Shimelis H, Moore RM, Feng B, Thomas A, Lindor NM, Polley EC, Goldgar DE, Iversen E, Monteiro ANA, Suman VJ, Couch FJ.
    • Genet Med. 2019 Jan;21(1):71-80. doi: 10.1038/s41436-018-0018-4. Epub 2018 Jun 8.
    • Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk.
    • Petitalot A, Dardillac E, Jacquet E, Nhiri N, Guirouilh-Barbat J, Julien P, Bouazzaoui I, Bonte D, Feunteun J, Schnell JA, Lafitte P, Aude JC, Noguès C, Rouleau E, Lidereau R, Lopez BS, Zinn-Justin S, Caputo SM; UNICANCER Genetic Group BRCA network.
    • Mol Cancer Res. 2019 Jan;17(1):54-69. doi: 10.1158/1541-7786.MCR-17-0357. Epub 2018 Sep 26.
    • Functional evaluation of variants of unknown significance in the BRCA2 gene identified in genetic testing.
    • Heczkova M, Machackova E, Macinga P, Gallmeier E, Cahova M, Spicak J, Jirsa M, Foretova L, Hucl T.
    • Cancer Biol Ther. 2019;20(5):633-641. doi: 10.1080/15384047.2018.1550566. Epub 2019 Jan 13.
    • BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2.
    • Cline MS, Liao RG, Parsons MT, Paten B, Alquaddoomi F, Antoniou A, Baxter S, Brody L, Cook-Deegan R, Coffin A, Couch FJ, Craft B, Currie R, Dlott CC, Dolman L, den Dunnen JT, Dyke SOM, Domchek SM, Easton D, Fischmann Z, Foulkes WD, Garber J, Goldgar D, Goldman MJ, Goodhand P, Harrison S, Haussler D, Kato K, Knoppers B, Markello C, Nussbaum R, Offit K, Plon SE, Rashbass J, Rehm HL, Robson M, Rubinstein WS, Stoppa-Lyonnet D, Tavtigian S, Thorogood A, Zhang C, Zimmermann M; BRCA Challenge Authors, Burn J, Chanock S, Rätsch G, Spurdle AB.
    • PLoS Genet. 2018 Dec 26;14(12):e1007752. doi: 10.1371/journal.pgen.1007752. [Epub ahead of print]
    • BRCA1 and BRCA2 5' noncoding region variants identified in breast cancer patients alter promoter activity and protein binding.
    • Burke LJ, Sevcik J, Gambino G, Tudini E, Mucaki EJ, Shirley BC, Whiley P, Parsons MT, De Leeneer K, Gutiérrez-Enríquez S, Santamariña M, Caputo SM, Santana Dos Santos E, Soukupova J, Janatova M, Zemankova P, Lhotova K, Stolarova L, Borecka M, Moles-Fernández A, Manoukian S, Bonanni B; ENIGMA Consortium, Edwards SL, Blok MJ, van Overeem Hansen T, Rossing M, Diez O, Vega A, Claes KBM, Goldgar DE, Rouleau E, Radice P, Peterlongo P, Rogan PK, Caligo M, Spurdle AB, Brown MA.
    • Hum Mutat. 2018 Dec;39(12):2025-2039. doi: 10.1002/humu.23652. Epub 2018 Sep 24.
    • Reclassification of BRCA1 and BRCA2 variants of uncertain significance: a multifactorial analysis of multicentre prospective cohort.
    • Lee JS, Oh S, Park SK, Lee MH, Lee JW, Kim SW, Son BH, Noh DY, Lee JE, Park HL, Kim MJ, Cho SI, Lee YK, Park SS, Seong MW.
    • J Med Genet. 2018 Dec;55(12):794-802. doi: 10.1136/jmedgenet-2018-105565. Epub 2018 Nov 10.
    • Big Data Sharing: A Crucial Democratic Issue for Genomic Medicine.
    • Derbez B.
    • Front Public Health. 2018 Nov 28;6:334. doi: 10.3389/fpubh.2018.00334. eCollection 2018.
    • Screening of BRCA1/2 deep intronic regions by targeted gene sequencing identifies the first germline BRCA1 variant causing pseudoexon activation in a patient with breast/ovarian cancer.
    • Montalban G, Bonache S, Moles-Fernández A, Gisbert-Beamud A, Tenés A, Bach V, Carrasco E, López-Fernández A, Stjepanovic N, Balmaña J, Diez O, Gutiérrez-Enríquez S.
    • J Med Genet. 2018 Nov 24. pii: jmedgenet-2018-105606. doi: 10.1136/jmedgenet-2018-105606. [Epub ahead of print]
    • Case report
    • Trans-activation-based risk assessment of BRCA1 BRCT variants with unknown clinical significance.
    • Langerud J, Jarhelle E, Van Ghelue M, Ariansen SL, Iversen N.
    • Hum Genomics. 2018 Nov 20;12(1):51. doi: 10.1186/s40246-018-0183-1.
    • Non-Coding Variants in BRCA1 and BRCA2 Genes: Potential Impact on Breast and Ovarian Cancer Predisposition.
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    Research News: Gene editing reveals the effect of thousands of variants in a key cancer gene (Nature)

    Research News: A CRISPR Approach for Accurately Classifying BRCA1 Variants. (Medscape Oncology)

    Research News: A new method for determining whether genetic variants in BRCA1 increase cancer risk. (FORCE XRAYS)

    Research news:

    Technique Pinpoints Oncogenic BRCA1 Mutations.

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    • Evaluation of some direct-to-consumer genetic testing reveals inaccuracies and misinterpretations.
    • [No author given]
    • FORCE. XRAYS. 2018 Jun 28.

    False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care.

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    Commentary:

    Attention: Direct-To-Consumer patrons: Proceed with caution.

    Research news: Evaluation of some direct-to-consumer genetic testing reveals inaccuracies and misinterpretations (FORCE. XRAYS.)

    Press: Wrangle Over DTC Results—Ambry Study Highlights 40% False Positives, 23andMe Defends Tests, and Experts Weigh In. (Clinical OMICs)

    Press: Ambry and My Gene Counsel Team Up on Tests to Confirm DTC Results, Counseling. (Clinical OMICs)

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    Letter, Comment:

    ClinVar Is a Critical Resource to Advance Variant Interpretation.

    Letter, Reply:

    In Reply.

    • BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer.
    • Shimelis H, Mesman RLS, Von Nicolai C, Ehlen A, Guidugli L, Martin C, Calléja FMGR, Meeks H, Hallberg E, Hinton J, Lilyquist J, Hu C, Aalfs CM, Aittomäki K, Andrulis I, Anton-Culver H, Arndt V, Beckmann MW, Benitez J, Bogdanova NV, Bojesen SE, Bolla MK, Borresen-Dale AL, Brauch H, Brennan P, Brenner H, Broeks A, Brouwers B, Brüning T, Burwinkel B, Chang-Claude J, Chenevix-Trench G, Cheng CY3, Choi JY, Collée JM, Cox A, Cross SS, Czene K, Darabi H, Dennis J, Dörk T, Dos-Santos-Silva I, Dunning AM, Fasching PA, Figueroa J, Flyger H, García-Closas M, Giles GG, Glendon G, Guénel P, Haiman CA, Hall P, Hamann U, Hartman M, Hogervorst FB, Hollestelle A, Hopper JL, Ito H, Jakubowska A, Kang D, Kosma VM, Kristensen V, Lai KN, Lambrechts D, Marchand LL, Li J, Lindblom A, Lophatananon A, Lubinski J, Machackova E, Mannermaa A, Margolin S, Marme F, Matsuo K, Miao H, Michailidou K, Milne RL, Muir K, Neuhausen SL, Nevanlinna H, Olson JE, Olswold C, Oosterwijk JJC, Osorio A, Peterlongo P, Peto J, Pharoah PDP, Pylkäs K, Radice P, Rashid MU, Rhenius V, Rudolph A, Sangrajrang S, Sawyer EJ, Schmidt MK, Schoemaker MJ, Seynaeve C, Shah M, Shen CY, Shrubsole M, Shu XO, Slager S, Southey MC, Stram DO, Swerdlow A, Teo SH, Tomlinson I, Torres D, Truong T, van Asperen CJ, van der Kolk LE, Wang Q, Winqvist R, Wu AH, Yu JC, Zheng W, Zheng Y, Leary J, Walker L, Foretova L, Fostira F, Claes KBM, Varesco L, Moghadasi S, Easton DF, Spurdle A, Devilee P, Vrieling H, Monteiro ANA, Goldgar DE, Carreira A, Vreeswijk MPG, Couch FJ; for kConFab/AOCS Investigators; for NBCS Collaborators.
    • Cancer Res. 2017 Jun 1;77(11):2789-2799. doi: 10.1158/0008-5472.CAN-16-2568. Epub 2017 Mar 10.
    • Validation and optimization of the Ion Torrent S5 XL sequencer and Oncomine workflow for BRCA1 and BRCA2 genetic testing.
    • Shin S, Kim Y, Oh SC, Yu N, Lee ST, Choi JR, Lee KA.
    • Oncotarget. 2017 May 23;8(21):34858-34866. doi: 10.18632/oncotarget.16799.
    • Power of pedigree likelihood analysis in extended pedigrees to classify rare variants of uncertain significance in cancer risk genes.
    • Rosenthal EA, Ranola JMO, Shirts BH.
    • Fam Cancer. 2017 May 22. doi: 10.1007/s10689-017-9989-6. [Epub ahead of print]
    • Variant effect prediction tools assessed using independent, functional assay-based datasets: implications for discovery and diagnostics.
    • Mahmood K, Jung CH, Philip G, Georgeson P, Chung J, Pope BJ, Park DJ.
    • Hum Genomics. 2017 May 16;11(1):10. doi: 10.1186/s40246-017-0104-8.
    • [China expert consensus on BRCA variant interpretation].
    • Panel members of China expert consensus on BRCA variant interpretation.
    • Zhonghua Bing Li Xue Za Zhi. 2017 May 8;46(5):293-297. doi: 10.3760/cma.j.issn.0529-5807.2017.05.002.
    • [Article in Chinese]
    • Assessment of in silico protein sequence analysis in the clinical classification of variants in cancer risk genes.
    • Kerr ID, Cox HC, Moyes K, Evans B, Burdett BC, van Kan A, McElroy H, Vail PJ, Brown KL, Sumampong DB, Monteferrante NJ, Hardman KL, Theisen A, Mundt E, Wenstrup RJ, Eggington JM.
    • J Community Genet. 2017 Apr;8(2):87-95. doi: 10.1007/s12687-016-0289-x. Epub 2017 Jan 3.
    • Functional classification of DNA variants by hybrid minigenes: Identification of 30 spliceogenic variants of BRCA2 exons 17 and 18.
    • Fraile-Bethencourt E, Díez-Gómez B, Velásquez-Zapata V, Acedo A, Sanz DJ, Velasco EA.
    • PLoS Genet. 2017 Mar 24;13(3):e1006691. doi: 10.1371/journal.pgen.1006691. eCollection 2017 Mar.
    • Characterization of BRCA1 and BRCA2 variants found in a Norwegian breast or ovarian cancer cohort.
    • Jarhelle E, Riise Stensland HM, Mæhle L, Van Ghelue M.
    • Fam Cancer. 2017 Jan;16(1):1-16. doi: 10.1007/s10689-016-9916-2.
    • A Lens for Evaluating Genetic Information Governance Models: Balancing Equity, Efficiency and Sustainability.
    • Skorve E, Vassilakopoulou P, Aanestad M, Grünfeld T.
    • Stud Health Technol Inform. 2017;235:298-302.
    • A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA.
    • Esposito MV, Nunziato M, Starnone F, Telese A, Calabrese A, D'Aiuto G, Pucci P, D'Aiuto M, Baralle F, D'Argenio V, Salvatore F.
    • Int J Mol Sci. 2016 Dec 21;17(12). pii: E2145. doi: 10.3390/ijms17122145.
    • Yeast cells reveal the misfolding and the cellular mislocalisation of the human BRCA1 protein.
    • Thouvenot P, Fourrière L, Dardillac E, Ben Yamin B, Lescure A, Lejour V, Heiligenstein X, Boulé JB, Romao M, Raposo-Benedetti G, Lopez BS, Nicolas A, Millot GA.
    • J Cell Sci. 2016 Dec 1;129(23):4366-4378. Epub 2016 Oct 17.

    "In This Issue":

    Yeast cells detect human BRCA1 misfolding.

    • BRCA Share: A Collection of Clinical BRCA Gene Variants.
    • Beroud C, Letovsky SI, Braastad CD, Caputo SM, Beaudoux O, Bignon YJ, De Paillerets BB, Bronner M, Buell CM, Collod-Béroud G, Coulet F, Derive N, Divincenzo C, Elzinga CD, Garrec C, Houdayer C, Karbassi I, Lizard S, Love A, Muller D, Nagan N, Nery CR, Rai G, Revillion F, Salgado D, Sévenet N, Sinilnikova O, Sobol H, Stoppa-Lyonnet D, Toulas C, Trautman E, Vaur D, Vilquin P, Weymouth KS, Willis A; Laboratory Corporation of America Variant Classification Group; Quest Diagnostics Variant Classification Group; UNICANCER Genetic Group BRCA Laboratory Network, Eisenberg M, Strom CM.
    • Hum Mutat. 2016 Dec;37(12):1318-1328. doi: 10.1002/humu.23113. Epub 2016 Sep 28.
    • Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing.
    • Balmaña J, Digiovanni L, Gaddam P, Walsh MF, Joseph V, Stadler ZK, Nathanson KL, Garber JE, Couch FJ, Offit K, Robson ME, Domchek SM.
    • J Clin Oncol. 2016 Dec;34(34):4071-4078. Epub 2016 Sep 30.

    Letter:

    Clinical Genetics Testing Laboratories Have a Remarkably Low Rate of Clinically Significant Discordance When Interpreting Variants in Hereditary Cancer Syndrome Genes.

    Letter:

    Reply to R. Nussbaum et al and J. Dolinsky et al.

    • As revenue falls, a pioneer of cancer gene testing slams rivals with overblown claims.
    • Sharon Begley
    • STAT. 2016 Nov 29.

    Comments from NSGC Discussion Forum Cancer SIG

    Subject: Variant calling

    • Revisiting the morbid genome of Mendelian disorders.
    • Abouelhoda M, Faquih T, El-Kalioby M, Alkuraya FS.
    • Genome Biol. 2016 Nov 24;17(1):235.
    • In silico, in vitro and case-control analyses as an effective combination for analyzing BRCA1 and BRCA2 unclassified variants in a population-based sample.
    • Rodríguez-Balada M, Roig B, Martorell L, Melé M, Salvat M, Vilella E, Borràs J, Gumà J.
    • Cancer Genet. 2016 Nov;209(11):487-492. doi: 10.1016/j.cancergen.2016.09.003. Epub 2016 Sep 20.
    • Sensitivity of BRCA1/2 testing in high-risk breast/ovarian/male breast cancer families: little contribution of comprehensive RNA/NGS panel testing.
    • Byers H, Wallis Y, van Veen EM, Lalloo F, Reay K, Smith P, Wallace AJ, Bowers N, Newman WG, Evans DG.
    • Eur J Hum Genet. 2016 Nov;24(11):1591-1597. doi: 10.1038/ejhg.2016.57. Epub 2016 Jun 8.
    • HIPAA complaint alleges myriad genetics withheld variant data from patients: Allegation highlights the importance of data sharing, new HIPAA guidance.
    • [No authors listed]
    • Am J Med Genet A. 2016 Sep;170(9):2234-5. doi: 10.1002/ajmg.a.37886.
    • Molecular characterization, homology modeling and docking studies of the R2787H missense variation in BRCA2 gene: Association with breast cancer.
    • Riahi A, Messaoudi A, Mrad R, Fourati A, Chabouni-Bouhamed H, Kharrat M.
    • J Theor Biol. 2016 Aug 21;403:188-96. doi: 10.1016/j.jtbi.2016.05.013. Epub 2016 May 19.
    • Multi-gene Testing Increases Complexity of Counseling Women at Risk of Breast and Ovarian Cancer.
    • Hughes, D
    • Cancer Therapy Advisor. Breast Cancer Advisor. 2016 Jul 6.

    Comments from NSGC Discussion Forum Cancer SIG

    Subject: VUS

    • Adding In Silico Assessment of Potential Splice Aberration to the Integrated Evaluation of BRCA Gene Unclassified Variants.
    • Vallée MP, Di Sera TL, Nix DA, Paquette AM, Parsons MT, Bell R, Hoffman A, Hogervorst FB, Goldgar DE, Spurdle AB, Tavtigian SV.
    • Hum Mutat. 2016 Jul;37(7):627-39. doi: 10.1002/humu.22973. Epub 2016 Apr 15.
    • Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations.
    • Caminsky NG, Mucaki EJ, Perri AM, Lu R, Knoll JH, Rogan PK.
    • Hum Mutat. 2016 Jul;37(7):640-52. doi: 10.1002/humu.22972. Epub 2016 Mar 18.
    • Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making.
    • Thouvenot P, Ben Yamin B, Fourrière L, Lescure A, Boudier T, Del Nery E, Chauchereau A, Goldgar DE, Houdayer C, Stoppa-Lyonnet D, Nicolas A, Millot GA.
    • PLoS Genet. 2016 Jun 6;12(6):e1006096. doi: 10.1371/journal.pgen.1006096. eCollection 2016.
    • Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms.
    • de la Hoya M, Soukarieh O, López-Perolio I, Vega A, Walker LC, van Ierland Y, Baralle D, Santamariña M, Lattimore V, Wijnen J, Whiley P, Blanco A, Raponi M, Hauke J, Wappenschmidt B, Becker A, Hansen TV, Behar R, Investigators K, Niederacher D, Arnold N, Dworniczak B, Steinemann D, Faust U, Rubinstein W, Hulick PJ, Houdayer C, Caputo SM, Castera L, Pesaran T, Chao E, Brewer C, Southey MC, van Asperen CJ, Singer CF, Sullivan J, Poplawski N, Mai P, Peto J, Johnson N, Burwinkel B, Surowy H, Bojesen SE, Flyger H, Lindblom A, Margolin S, Chang-Claude J, Rudolph A, Radice P, Galastri L, Olson JE, Hallberg E, Giles GG, Milne RL, Andrulis IL, Glendon G, Hall P, Czene K, Blows F, Shah M, Wang Q, Dennis J, Michailidou K, McGuffog L, Bolla MK, Antoniou AC, Easton DF, Couch FJ, Tavtigian S, Vreeswijk MP, Parsons M, Meeks HD, Martins A, Goldgar DE, Spurdle AB.
    • Hum Mol Genet. 2016 Jun 1;25(11):2256-2268. Epub 2016 Mar 23.
    • Exclusive: Breast cancer gene database gives clearer picture of risk.
    • Susan Miller.
    • USA Today. 2016 Jun 1.
    • Multigene testing of moderate-risk genes: be mindful of the missense.
    • Young EL, Feng BJ, Stark AW, Damiola F, Durand G, Forey N, Francy TC, Gammon A, Kohlmann WK, Kaphingst KA, McKay-Chopin S, Nguyen-Dumont T, Oliver J, Paquette AM, Pertesi M, Robinot N, Rosenthal JS, Vallee M, Voegele C, Hopper JL, Southey MC, Andrulis IL, John EM, Hashibe M, Gertz J; Breast Cancer Family Registry, Le Calvez-Kelm F, Lesueur F, Goldgar DE, Tavtigian SV.
    • J Med Genet. 2016 Jun;53(6):366-76. doi: 10.1136/jmedgenet-2015-103398. Epub 2016 Jan 19.
    • Variant classifications in BRCA1 and BRCA2: A systematic analysis of interlaboratory concordance.
    • Lincoln SE, Cline M, Yang S, Kobayashi Y, Zhang M, O'Leary E, Topper S, Paten B, Nussbaum R.
    • J Clin Oncol. 2016 May 20;34(15s):1592.
    • Conference abstract
    • Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.
    • Maxwell KN, Hart SN, Vijai J, Schrader KA, Slavin TP, Thomas T, Wubbenhorst B, Ravichandran V, Moore RM, Hu C, Guidugli L, Wenz B, Domchek SM, Robson ME, Szabo C, Neuhausen SL, Weitzel JN, Offit K, Couch FJ, Nathanson KL.
    • Am J Hum Genet. 2016 May 5;98(5):801-817. doi: 10.1016/j.ajhg.2016.02.024.
    • A unified analytic framework for prioritization of non-coding variants of uncertain significance in heritable breast and ovarian cancer.
    • Mucaki EJ, Caminsky NG, Perri AM, Lu R, Laederach A, Halvorsen M, Knoll JH, Rogan PK.
    • BMC Med Genomics. 2016 Apr 11;9(1):19. doi: 10.1186/s12920-016-0178-5.
    • Classification and Clinical Management of Variants of Uncertain Significance in High Penetrance Cancer Predisposition Genes.
    • Moghadasi S, Eccles DM, Devilee P, Vreeswijk MP, van Asperen CJ.
    • Hum Mutat. 2016 Apr;37(4):331-6. doi: 10.1002/humu.22956. Epub 2016 Feb 5.
    • Editorial / Commentary
    • Medical implications of technical accuracy in genome sequencing.
    • Goldfeder RL, Priest JR, Zook JM, Grove ME, Waggott D, Wheeler MT, Salit M, Ashley EA.
    • Genome Med. 2016 Mar 2;8(1):24. doi: 10.1186/s13073-016-0269-0.
    • Beyond DNA: An Integrated and Functional Approach for Classifying Germline Variants in Breast Cancer Genes.
    • Pesaran T, Karam R, Huether R, Li S, Farber-Katz S, Chamberlin A, Chong H, LaDuca H, Elliott A.
    • Int J Breast Cancer. 2016;2016:2469523. Epub 2016 Oct 16.
    • BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers.
    • Meeks HD, Song H, Michailidou K, Bolla MK, Dennis J, Wang Q, Barrowdale D, Frost D; EMBRACE, McGuffog L, Ellis S, Feng B, Buys SS, Hopper JL, Southey MC, Tesoriero A; kConFab Investigators, James PA, Bruinsma F, Campbell IG; Australia Ovarian Cancer Study Group, Broeks A, Schmidt MK, Hogervorst FB; HEBON, Beckman MW, Fasching PA, Fletcher O, Johnson N, Sawyer EJ, Riboli E, Banerjee S, Menon U, Tomlinson I, Burwinkel B, Hamann U, Marme F, Rudolph A, Janavicius R, Tihomirova L, Tung N, Garber J, Cramer D, Terry KL, Poole EM, Tworoger SS, Dorfling CM, van Rensburg EJ, Godwin AK, Guénel P, Truong T; GEMO Study Collaborators, Stoppa-Lyonnet D, Damiola F, Mazoyer S, Sinilnikova OM, Isaacs C, Maugard C, Bojesen SE, Flyger H, Gerdes AM, Hansen TV, Jensen A, Kjaer SK, Hogdall C, Hogdall E, Pedersen IS, Thomassen M, Benitez J, González-Neira A, Osorio A, Hoya Mde L, Segura PP, Diez O, Lazaro C, Brunet J, Anton-Culver H, Eunjung L, John EM, Neuhausen SL, Ding YC, Castillo D, Weitzel JN, Ganz PA, Nussbaum RL, Chan SB, Karlan BY, Lester J, Wu A, Gayther S, Ramus SJ, Sieh W, Whittermore AS, Monteiro AN, Phelan CM, Terry MB, Piedmonte M, Offit K, Robson M, Levine D, Moysich KB, Cannioto R, Olson SH, Daly MB, Nathanson KL, Domchek SM, Lu KH, Liang D, Hildebrant MA, Ness R, Modugno F, Pearce L, Goodman MT, Thompson PJ, Brenner H, Butterbach K, Meindl A, Hahnen E, Wappenschmidt B, Brauch H, Brüning T, Blomqvist C, Khan S, Nevanlinna H, Pelttari LM, Aittomäki K, Butzow R, Bogdanova NV, Dörk T, Lindblom A, Margolin S, Rantala J, Kosma VM, Mannermaa A, Lambrechts D, Neven P, Claes KB, Maerken TV, Chang-Claude J, Flesch-Janys D, Heitz F, Varon-Mateeva R, Peterlongo P, Radice P, Viel A, Barile M, Peissel B, Manoukian S, Montagna M, Oliani C, Peixoto A, Teixeira MR, Collavoli A, Hallberg E, Olson JE, Goode EL, Hart SN, Shimelis H, Cunningham JM, Giles GG, Milne RL, Healey S, Tucker K, Haiman CA, Henderson BE, Goldberg MS, Tischkowitz M, Simard J, Soucy P, Eccles DM, Le N, Borresen-Dale AL, Kristensen V, Salvesen HB, Bjorge L, Bandera EV, Risch H, Zheng W, Beeghly-Fadiel A, Cai H, Pylkäs K, Tollenaar RA, Ouweland AM, Andrulis IL, Knight JA; OCGN, Narod S, Devilee P, Winqvist R, Figueroa J, Greene MH, Mai PL, Loud JT, García-Closas M, Schoemaker MJ, Czene K, Darabi H, McNeish I, Siddiquil N, Glasspool R, Kwong A, Park SK, Teo SH, Yoon SY, Matsuo K, Hosono S, Woo YL, Gao YT, Foretova L, Singer CF, Rappaport-Feurhauser C, Friedman E, Laitman Y, Rennert G, Imyanitov EN, Hulick PJ, Olopade OI, Senter L, Olah E, Doherty JA, Schildkraut J, Koppert LB, Kiemeney LA, Massuger LF, Cook LS, Pejovic T, Li J, Borg A, Öfverholm A, Rossing MA, Wentzensen N, Henriksson K, Cox A, Cross SS, Pasini BJ, Shah M, Kabisch M, Torres D, Jakubowska A, Lubinski J, Gronwald J, Agnarsson BA, Kupryjanczyk J, Moes-Sosnowska J, Fostira F, Konstantopoulou I, Slager S, Jones M; PRostate cancer AssoCiation group To Investigate Cancer Associated aLterations in the genome, Antoniou AC, Berchuck A, Swerdlow A, Chenevix-Trench G, Dunning AM, Pharoah PD, Hall P, Easton DF, Couch FJ, Spurdle AB, Goldgar DE.
    • J Natl Cancer Inst. 2015 Nov 19;108(2). pii: djv315. doi: 10.1093/jnci/djv315. Print 2016 Feb.

    Comments on NSGC Discussion Forum Cancer SIG

    Subject: BRCA2 c.9976A>T classification

    • A workflow for the detection and classification of variants in the BRCA1 and BRCA2 genes.
    • Nickerson SL, Lai SW, Tang R, Prosser DO, Love DR.
    • Pathology. 2016 Feb;48 Suppl 1:S96. doi: 10.1016/j.pathol.2015.12.272. Epub 2016 Feb 25.
    • Exonic Splicing Mutations Are More Prevalent than Currently Estimated and Can Be Predicted by Using In Silico Tools.
    • Soukarieh O, Gaildrat P, Hamieh M, Drouet A, Baert-Desurmont S, Frébourg T, Tosi M, Martins A.
    • PLoS Genet. 2016 Jan 13;12(1):e1005756. doi: 10.1371/journal.pgen.1005756. eCollection 2016.

    Research Highlight

    RNA: Exonic splicing mutation prevalence.

    • Investigating the effect of 28 BRCA1 and BRCA2 mutations on their related transcribed mRNA.
    • Quiles F, Menéndez M, Tornero E, del Valle J, Teulé À, Palanca S, Izquierdo A, Gómez C, Campos O, Santamaria R, Brunet J, Capellá G, Feliubadaló L, Lázaro C.
    • Breast Cancer Res Treat. 2016 Jan;155(2):215-22. doi: 10.1007/s10549-015-3674-y. Epub 2016 Jan 6.
    • Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance.
    • Woods NT, Baskin R, Golubeva V, Jhuraney A, De-Gregoriis G, Vaclova T, Goldgar DE, Couch FJ, Carvalho MA, Iversen ES, Monteiro AN.
    • NPJ Genom Med. 2016;1. pii: 16001. doi: 10.1038/npjgenmed.2016.1. Epub 2016 Mar 2.
    • DATA SHARING AND REPRODUCIBLE CLINICAL GENETIC TESTING: SUCCESSES AND CHALLENGES.
    • Yang S, Cline M, Zhang C, Paten B, Lincoln SE.
    • Pac Symp Biocomput. 2016;22:166-176.
    • Patterns and functional implications of rare germline variants across 12 cancer types.
    • Lu C, Xie M, Wendl MC, Wang J, McLellan MD, Leiserson MD, Huang KL, Wyczalkowski MA, Jayasinghe R, Banerjee T, Ning J, Tripathi P, Zhang Q, Niu B, Ye K, Schmidt HK, Fulton RS, McMichael JF, Batra P, Kandoth C, Bharadwaj M, Koboldt DC, Miller CA, Kanchi KL, Eldred JM, Larson DE, Welch JS, You M, Ozenberger BA, Govindan R, Walter MJ, Ellis MJ, Mardis ER, Graubert TA, Dipersio JF, Ley TJ, Wilson RK, Goodfellow PJ, Raphael BJ, Chen F, Johnson KJ, Parvin JD, Ding L.
    • Nat Commun. 2015 Dec 22;6:10086. doi: 10.1038/ncomms10086.

    Press: Study Uncovers Inherited Genetic Susceptibility Across 12 Cancer Types? (DoveMed)

    • DNA methylation profiling to assess pathogenicity of BRCA1 unclassified variants in breast cancer.
    • Flower KJ, Shenker NS, El-Bahrawy M, Goldgar DE, Parsons MT; KConFab Investigators; Affect study group, Spurdle AB, Morris JR, Brown R, Flanagan JM.
    • Epigenetics. 2015 Dec 2;10(12):1121-32. doi: 10.1080/15592294.2015.1111504.
    • Exceptions to the rule: Case studies in the prediction of pathogenicity for genetic variants in hereditary cancer genes.
    • Rosenthal ET, Bowles KR, Pruss D, van Kan A, Vail PJ, McElroy H, Wenstrup RJ.
    • Clin Genet. 2015 Dec;88(6):533-41. doi: 10.1111/cge.12560. Epub 2015 Feb 11.
    • Functional Analysis of BARD1 Missense Variants in Homology-Directed Repair of DNA Double Strand Breaks.
    • Lee C, Banerjee T, Gillespie J, Ceravolo A, Parvinsmith MR, Starita LM, Fields S, Toland AE, Parvin JD.
    • Hum Mutat. 2015 Dec;36(12):1205-14. doi: 10.1002/humu.22902. Epub 2015 Sep 22.
    • Comparison of locus-specific databases for BRCA1 and BRCA2 variants reveals disparity in variant classification within and among databases.
    • Vail PJ, Morris B, van Kan A, Burdett BC, Moyes K, Theisen A, Kerr ID, Wenstrup RJ, Eggington JM.
    • J Community Genet. 2015 Oct;6(4):351-9. doi: 10.1007/s12687-015-0220-x. Epub 2015 Mar 18.
    • ClinGen and Genetic Testing.
    • Karam R, Pesaran T, Chao E.
    • N Engl J Med. 2015 Oct;373(14):1376-7. doi: 10.1056/NEJMc1508700#SA1.

    ClinGen--the Clinical Genome Resource.

    Gene-panel sequencing and the prediction of breast-cancer risk.

    Comment / Letter

    ClinGen and Genetic Testing.

    Comment / Letter

    ClinGen and Genetic Testing.

    • Functional isogenic modeling of BRCA1 alleles reveals distinct carrier phenotypes.
    • Cochran RL, Cidado J, Kim M, Zabransky DJ, Croessmann S, Chu D, Wong HY, Beaver JA, Cravero K, Erlanger B, Parsons H, Heaphy CM, Meeker AK, Lauring J, Park BH.
    • Oncotarget. 2015 Sep 22;6(28):25240-51. doi: 10.18632/oncotarget.4595.
    • Meeting the challenges of interpreting variants of unknown clinical significance in BRCA testing.
    • Lattimore V, Currie M, Lintott C, Sullivan J, Robinson BA, Walker LC.
    • N Z Med J. 2015 Aug 7;128(1419):56-61.
    • Curating the Way to Better Determinants of Genetic Risk.
    • Phimister EG.
    • N Engl J Med. 2015 Jun 4;372(23):2227-2228. Epub 2015 May 27.
    • Editorial / Commentary
    • Gene-Panel Sequencing and the Prediction of Breast-Cancer Risk.
    • Easton DF, Pharoah PD, Antoniou AC, Tischkowitz M, Tavtigian SV, Nathanson KL, Devilee P, Meindl A, Couch FJ, Southey M, Goldgar DE, Evans DG, Chenevix-Trench G, Rahman N, Robson M, Domchek SM, Foulkes WD.
    • N Engl J Med. 2015 Jun 4;372(23):2243-2257. Epub 2015 May 27.

    Comments on NSGC Discussion Forum Cancer SIG

    Subject: Excellent review paper in NEJM

    Comment / Letter

    ClinGen and Genetic Testing.

    • Functional variant analyses (FVAs) predict pathogenicity in the BRCA1 DNA double-strand break repair pathway.
    • Loke J, Pearlman A, Upadhyay K, Tesfa L, Shao Y, Ostrer H.
    • Hum Mol Genet. 2015 Jun 1;24(11):3030-7. doi: 10.1093/hmg/ddv048. Epub 2015 Feb 4.
    • Massively Parallel Functional Analysis of BRCA1 RING Domain Variants.
    • Starita LM, Young DL, Islam M, Kitzman JO, Gullingsrud J, Hause RJ, Fowler DM, Parvin JD, Shendure J, Fields S.
    • Genetics. 2015 Jun;200(2):413-22. doi: 10.1534/genetics.115.175802. Epub 2015 Mar 30.

    Press: Study demonstrates potential of new approach for sorting out BRCA1 gene variants. (News Medical)

    • Behind the Scenes of Breast Cancer, Researchers Collect Genetic Clues in BRCA Database.
    • [No author given]
    • GlobeNewswire. 2015 May 7.
    • Predicting the Pathogenic Potential of BRCA1 and BRCA2 Gene Variants Identified in Clinical Genetic Testing.
    • Brookes C, Lai S, Doherty E, Love DR.
    • Sultan Qaboos Univ Med J. 2015 May;15(2):e218-25. Epub 2015 May 28.
    • BRCA Share (formerly UMD-BRCA1 mutations database) Home.
    • [No author given]
    • BRCA Share™ (formerly UMD-BRCA1 mutations database). 2015 Apr 21.
    • Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic.
    • Ahlborn LB, Dandanell M, Steffensen AY, Jønson L, Nielsen FC, Hansen TV.
    • Breast Cancer Res Treat. 2015 Apr;150(2):289-98. doi: 10.1007/s10549-015-3313-7. Epub 2015 Feb 28.
    • Characterization of three alternative transcripts of the BRCA1 gene in patients with breast cancer and a family history of breast and/or ovarian cancer who tested negative for pathogenic mutations.
    • Gambino G, Tancredi M, Falaschi E, Aretini P, Caligo MA.
    • Int J Mol Med. 2015 Apr;35(4):950-6. doi: 10.3892/ijmm.2015.2103. Epub 2015 Feb 16.
    • BRCA1 Circos: a visualisation resource for functional analysis of missense variants.
    • Jhuraney A, Velkova A, Johnson RC, Kessing B, Carvalho RS, Whiley P, Spurdle AB, Vreeswijk MP, Caputo SM, Millot GA, Vega A, Coquelle N, Galli A, Eccles D, Blok MJ, Pal T, van der Luijt RB, Santamariña Pena M, Neuhausen SL, Donenberg T, Machackova E, Thomas S, Vallée M, Couch FJ, Tavtigian SV, Glover JN, Carvalho MA, Brody LC, Sharan SK, Monteiro AN; Evidence-based Network for the Interpretation of Germline Mutant Alleles Consortium.
    • J Med Genet. 2015 Apr;52(4):224-30. doi: 10.1136/jmedgenet-2014-102766. Epub 2015 Feb 2.
    • Functional Classification of BRCA2 DNA Variants by Splicing Assays in a Large Minigene with 9 Exons.
    • Acedo A, Hernández-Moro C, Curiel-García Á, Díez-Gómez B, Velasco EA.
    • Hum Mutat. 2015 Feb;36(2):210-21. doi: 10.1002/humu.22725.
    • Genome Annotation by Shotgun Inactivation of a Native Gene in Hemizygous Cells: Application to BRCA2 with Implication of Hypomorphic Variants.
    • Ghosh S, Bhunia AK, Paun BC, Gilbert SF, Dhru U, Patel K, Kern SE.
    • Hum Mutat. 2015 Feb;36(2):260-9. doi: 10.1002/humu.22736.

    In This Issue"

    Shotgun approach to functional annotation of genes.

    • Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia.
    • Spurdle AB, Couch FJ, Parsons MT, McGuffog L, Barrowdale D, Bolla MK, Wang Q, Healey S, Schmutzler R, Wappenschmidt B, Rhiem K, Hahnen E, Engel C, Meindl A, Ditsch N, Arnold N, Plendl H, Niederacher D, Sutter C, Wang-Gohrke S, Steinemann D, Preisler-Adams S, Kast K, Varon-Mateeva R, Ellis S, Frost D, Platte R, Perkins J, Evans D, Izatt L, Eeles R, Adlard J, Davidson R, Cole T, Scuvera G, Manoukian S, Bonanni B, Mariette F, Fortuzzi S, Viel A, Pasini B, Papi L, Varesco L, Balleine R, Nathanson KL, Domchek SM, Offitt K, Jakubowska A, Lindor N, Thomassen M, Jensen U, Rantala J, Borg Å, Andrulis IL, Miron A, Hansen T, Caldes T, Neuhausen SL, Toland AE, Nevanlinna H, Montagna M, Garber J, Godwin AK, Osorio A, Factor RE, Terry MB, Rebbeck TR, Karlan BY, Southey M, Rashid M, Tung N, Pharoah P, Blows FM, Dunning AM, Provenzano E, Hall P, Czene K, Schmidt MK, Broeks A, Cornelissen S, Verhoef S, Fasching PA, Beckmann MW, Ekici AB, Slamon DJ, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Chang-Claude J, Flesch-Janys D, Rudolph A, Seibold P, Aittomäki K, Muranen TA, Heikkilä P, Blomqvist C, Figueroa J, Chanock SJ, Brinton L, Lissowska J, Olson JE, Pankratz VS, John EM, Whittemore AS, West DW, Hamann U, Torres D, Ulmer H, Rüdiger T, Devilee P, Tollenaar R, Seynaeve C, Van Asperen CJ, Eccles DM, Tapper WJ, Durcan L, Jones L, Peto J, Dos-Santos-Silva I, Fletcher O, Johnson N, Dwek M, Swann R, Bane AL, Glendon G, Mulligan AM, Giles GG, Milne RL, Baglietto L, McLean C, Carpenter J, Clarke C, Scott R, Brauch H, Brüning T, Ko YD, Cox A, Cross SS, Reed M, Lubinski J, Jaworska-Bieniek K, Durda K, Gronwald J, Dörk T, Bogdanova N, Park-Simon TW, Hillemanns P, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Burwinkel B, Marme F, Surovy H, Yang R, Anton-Culver H, Ziogas A, Hooning MJ, Collée J, Martens J, Tilanus-Linthorst M, Brenner H, Dieffenbach A, Arndt V, Stegmaier C, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Lindblom A, Margolin S, Joseph V, Robson M, Rau-Murthy R, González-Neira A, Arias J, Zamora P, Benítez J, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Peterlongo P, Zaffaroni D, Barile M, Capra F, Radice P, Teo SH, Easton DF, Antoniou AC, Chenevix-Trench G, Goldgar DE; ABCTB Investigators; EMBRACE Group; GENICA Network; HEBON Group; kConFab Investigators.
    • Breast Cancer Res. 2014 Dec 23;16(6):3419. doi: 10.1186/s13058-014-0474-y.
    • Functional characterization of BRCA1 gene variants by mini-gene splicing assay.
    • Steffensen AY, Dandanell M, Jønson L, Ejlertsen B, Gerdes AM, Nielsen FC, Hansen TV.
    • Eur J Hum Genet. 2014 Dec;22(12):1362-1368. doi: 10.1038/ejhg.2014.40. Epub 2014 Mar 26.
    • An integrated in silico approach to analyze the involvement of single amino acid polymorphisms in FANCD1/BRCA2-PALB2 and FANCD1/BRCA2-RAD51 complex.
    • Doss CG, Nagasundaram N.
    • Cell Biochem Biophys. 2014 Nov;70(2):939-56. doi: 10.1007/s12013-014-0002-9.
    • An Efficient Pipeline for the Generation and Functional Analysis of Human BRCA2 Variants of Uncertain Significance.
    • Hendriks G, Morolli B, Calléja FM, Plomp A, Mesman RL, Meijers M, Sharan SK, Vreeswijk MP, Vrieling H.
    • Hum Mutat. 2014 Nov;35(11):1382-91. doi: 10.1002/humu.22678. Epub 2014 Sep 11.
    • Saturation editing of genomic regions by multiplex homology-directed repair.
    • Findlay GM, Boyle EA, Hause RJ, Klein JC, Shendure J.
    • Nature. 2014 Sep 4;513(7516):120-3. doi: 10.1038/nature13695.

    Comment:

    Biological techniques: Edit the genome to understand it.

    Comment:

    Deep mutational scans with targeted editing

    Comment:

    Technology: testing all possibilities.

    Press: Translating mutation to function: Genome editing may revolutionise how we interpret our genomes. (PHG Foundation)

    • A comprehensive laboratory-based program for classification of variants of uncertain significance in hereditary cancer genes.
    • Eggington JM, Bowles KR, Moyes K, Manley S, Esterling L, Sizemore S, Rosenthal E, Theisen A, Saam J, Arnell C, Pruss D, Bennett J, Burbidge LA, Roa B, Wenstrup RJ.
    • Clin Genet. 2014 Sep;86(3):229-37. doi: 10.1111/cge.12315. Epub 2013 Dec 20.

    Comments on NSGC Discussion Forum Cancer SIG

    Subject: PALB2 VUS

    Subject: MyRisk - anyone else feeling jipped?

    • Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes.
    • Pruss D, Morris B, Hughes E, Eggington JM, Esterling L, Robinson BS, van Kan A, Fernandes PH, Roa BB, Gutin A, Wenstrup RJ, Bowles KR.
    • Breast Cancer Res Treat. 2014 Aug;147(1):119-32. doi: 10.1007/s10549-014-3065-9. Epub 2014 Aug 2.
    • BRCA1 Exon 11, a CERES (Composite Regulatory Element of Splicing) Element Involved in Splice Regulation.
    • Tammaro C, Raponi M, Wilson DI, Baralle D.
    • Int J Mol Sci. 2014 Jul 23;15(7):13045-59. doi: 10.3390/ijms150713045.
    • BRCA1 Haploinsufficiency Leads to Altered Expression of Genes Involved in Cellular Proliferation and Development.
    • Feilotter HE, Michel C, Uy P, Bathurst L, Davey S.
    • PLoS One. 2014 Jun 20;9(6):e100068. doi: 10.1371/journal.pone.0100068. eCollection 2014.
    • The Truth about Public Genetic Databases.
    • [No author given]
    • Yale Cancer Genetic Counseling, 2014 Jun 16.
    • Cancer-gene data sharing boosted.
    • Hayden EC.
    • Nature. 2014 Jun 10;510(7504):198. doi: 10.1038/510198a.
    • Pathogenicity Evaluation of BRCA1 and BRCA2 Unclassified Variants Identified in Portuguese Breast/Ovarian Cancer Families.
    • Santos C, Peixoto A, Rocha P, Pinto P, Bizarro S, Pinheiro M, Pinto C, Henrique R, Teixeira MR.
    • J Mol Diagn. 2014 May;16(3):324-34. doi: 10.1016/j.jmoldx.2014.01.005. Epub 2014 Mar 5.
    • Estimating risks for variants of unknown significance according to their predicted pathogenicity classes with application to BRCA1.
    • Dowty JG, Lee E, McKean-Cowdin R, Henderson BE, Bernstein L, Ursin G, Hopper JL.
    • Breast Cancer Res Treat. 2014 Feb;144(1):171-7. doi: 10.1007/s10549-014-2845-6. Epub 2014 Jan 31.
    • Comparison of mRNA splicing assay protocols across multiple laboratories: recommendations for best practice in standardized clinical testing.
    • Whiley PJ, de la Hoya M, Thomassen M, Becker A, Brandão R, Pedersen IS, Montagna M, Menéndez M, Quiles F, Gutiérrez-Enríquez S, De Leeneer K, Tenés A, Montalban G, Tserpelis D, Yoshimatsu T, Tirapo C, Raponi M, Caldes T, Blanco A, Santamariña M, Guidugli L, de Garibay GR, Wong M, Tancredi M, Fachal L, Ding YC, Kruse T, Lattimore V, Kwong A, Chan TL, Colombo M, De Vecchi G, Caligo M, Baralle D, Lázaro C, Couch F, Radice P, Southey MC, Neuhausen S, Houdayer C, Fackenthal J, Hansen TV, Vega A, Diez O, Blok R, Claes K, Wappenschmidt B, Walker L, Spurdle AB, Brown MA; ENIGMA consortium.
    • Clin Chem. 2014 Feb;60(2):341-52. doi: 10.1373/clinchem.2013.210658. Epub 2013 Nov 8.
    • Functional Assays for Analysis of Variants of Uncertain Significance in BRCA2.
    • Guidugli L, Carreira A, Caputo SM, Ehlen A, Galli A, Monteiro AN, Neuhausen SL, Hansen TV, Couch FJ, Vreeswijk MP; ENIGMA consortium.
    • Hum Mutat. 2014 Feb;35(2):151-64. doi: 10.1002/humu.22478. Epub 2013 Dec 3.
    • Review
    • Multifactorial Likelihood Assessment of BRCA1 and BRCA2 Missense Variants Confirms That BRCA1:c.122A>G(p.His41Arg) Is a Pathogenic Mutation.
    • Whiley PJ, Parsons MT, Leary J, Tucker K, Warwick L, Dopita B, Thorne H, Lakhani SR, Goldgar DE, Brown MA, Spurdle AB.
    • PLoS One. 2014 Jan 28;9(1):e86836. doi: 10.1371/journal.pone.0086836. eCollection 2014.
    • Capillary Electrophoresis Analysis of Conventional Splicing Assays: IARC Analytical and Clinical Classification of 31 BRCA2 Genetic Variants.
    • de Garibay GR, Acedo A, García-Casado Z, Gutiérrez-Enríquez S, Tosar A, Romero A, Garre P, Llort G, Thomassen M, Díez O, Pérez-Segura P, Díaz-Rubio E, Velasco EA, Caldés T, de la Hoya M.
    • Hum Mutat. 2014 Jan;35(1):53-7. doi: 10.1002/humu.22456. Epub 2013 Oct 28.
    • Supreme Court Ruling Broadens BRCA Testing Options.
    • Azvolinsky A.
    • J Natl Cancer Inst. 2013 Nov 20;105(22):1671-2. doi: 10.1093/jnci/djt342. Epub 2013 Nov 6.
    • My Cancer Story, My Genes, My Information.
    • Joanna Rudnick.
    • Huffington Post. The Blog. 2013 Nov 19.
    • Functional Analysis of a Large set of BRCA2 exon 7 Variants Highlights the Predictive Value of Hexamer Scores in Detecting Alterations of Exonic Splicing Regulatory Elements
    • Di Giacomo D, Gaildrat P, Abuli A, Abdat J, Frébourg T, Tosi M, Martins A.
    • Hum Mutat. 2013 Nov;34(11):1547-1557. doi: 10.1002/humu.22428. Epub 2013 Sep 18.
    • A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants.
    • Bouwman P, van der Gulden H, van der Heijden I, Drost R, Klijn CN, Prasetyanti P, Pieterse M, Wientjens E, Seibler J, Hogervorst FB, Jonkers J.
    • Cancer Discov. 2013 Oct;3(10):1142-55. doi: 10.1158/2159-8290.CD-13-0094. Epub 2013 Jul 18.
    • Evaluation of a 5-tier scheme proposed for classification of sequence variants using bioinformatic and splicing assay data: inter-reviewer variability and promotion of minimum reporting guidelines.
    • Walker LC, Whiley PJ, Houdayer C, Hansen TV, Vega A, Santamarina M, Blanco A, Fachal L, Southey MC, Lafferty A, Colombo M, De Vecchi G, Radice P, Spurdle AB; ENIGMA consortium.
    • Hum Mutat. 2013 Oct;34(10):1424-31. doi: 10.1002/humu.22388. Epub 2013 Aug 13.
    • Meta-Analysis

    Introductory article:

    Classifying the Effects of BRCA1 and BRCA2 Variants on Splicing - A Systematic Study.

    • Functional analysis of BRCA1 missense variants of uncertain significance in Japanese breast cancer families.
    • Kawaku S, Sato R, Song H, Bando Y, Arinami T, Noguchi E.
    • J Hum Genet. 2013 Sep;58(9):618-21. doi: 10.1038/jhg.2013.71. Epub 2013 Jul 11.
    • Free the data: the end of genetic data as trade secrets.
    • Nguyen S, Terry SF.
    • Genet Test Mol Biomarkers. 2013 Aug;17(8):579-80. doi: 10.1089/gtmb.2013.1547.
    • Heritable genetic changes in the open.
    • [No authors listed]
    • Nat Methods. 2013 Aug;10(8):683.
    • Genomic Medicine Just Hit the Accelerator.
    • Eric J. Topol.
    • Medscape Internal Medicine. 2013 Jun 17.
    • Platform comparisons for identification of breast cancers with a BRCA-like copy number profile.
    • Schouten PC, van Dyk E, Braaf LM, Mulder L, Lips EH, de Ronde JJ, Holtman L, Wesseling J, Hauptmann M, Wessels LF, Linn SC, Nederlof PM.
    • Breast Cancer Res Treat. 2013 Jun;139(2):317-27. doi: 10.1007/s10549-013-2558-2. Epub 2013 May 14.
    • Missense variants of uncertain significance (VUS) altering the phosphorylation patterns of BRCA1 and BRCA2.
    • Tram E, Savas S, Ozcelik H.
    • PLoS One. 2013 May 21;8(5):e62468. doi: 10.1371/journal.pone.0062468. Print 2013.
    • Classifications within molecular subtypes enables identification of BRCA1/BRCA2 mutation carriers by RNA tumor profiling.
    • Larsen MJ, Kruse TA, Tan Q, Lænkholm AV, Bak M, Lykkesfeldt AE, Sørensen KP, Hansen TV, Ejlertsen B, Gerdes AM, Thomassen M.
    • PLoS One. 2013 May 21;8(5):e64268. doi: 10.1371/journal.pone.0064268. Print 2013.
    • Expression of human BRCA1Δ17-19 alternative splicing variant with a truncated BRCT domain in MCF-7 cells results in impaired assembly of DNA repair complexes and aberrant DNA damage response.
    • Sevcik J, Falk M, Macurek L, Kleiblova P, Lhota F, Hojny J, Stefancikova L, Janatova M, Bartek J, Stribrna J, Hodny Z, Jezkova L, Pohlreich P, Kleibl Z.
    • Cell Signal. 2013 May;25(5):1186-93. doi: 10.1016/j.cellsig.2013.02.008. Epub 2013 Feb 14.
    • BRCA1/2 Sequence Variants of Uncertain Significance: A Primer for Providers to Assist in Discussions and in Medical Management.
    • Lindor NM, Goldgar DE, Tavtigian SV, Plon SE, Couch FJ.
    • Oncologist. [2013 May;]18(5):518-24. doi: 10.1634/theoncologist.2012-0452. Epub 2013 Apr 24.
    • DNA Project Aims to Make Public a Company’s Data on Cancer Genes.
    • Gina Kolata.
    • NY Times. 2013 Apr 12.
    • Analysis of BRCA1 Variants in Double-Strand Break Repair by Homologous Recombination and Single-Strand Annealing.
    • Towler WI, Zhang J, Ransburgh DJ, Toland AE, Ishioka C, Chiba N, Parvin JD.
    • Hum Mutat. 2013 Mar;34(3):439-445. doi: 10.1002/humu.22251. Epub 2012 Dec 12.
    • Comparative in vitro and in silico analyses of variants in splicing regions of BRCA1 and BRCA2 genes and characterization of novel pathogenic mutations.
    • Colombo M, De Vecchi G, Caleca L, Foglia C, Ripamonti CB, Ficarazzi F, Barile M, Varesco L, Peissel B, Manoukian S, Radice P.
    • PLoS One. 2013;8(2):e57173. doi: 10.1371/journal.pone.0057173. Epub 2013 Feb 22.
    • Variants of Uncertain Significance in BRCA1 and BRCA2 assessment of in silico analysis and a proposal for communication in genetic counselling.
    • Moghadasi S, Hofland N, Wouts JN, Hogervorst FB, Wijnen JT, Vreeswijk MP, van Asperen CJ.
    • J Med Genet. 2013 Feb;50(2):74-9. doi: 10.1136/jmedgenet-2012-100961. Epub 2012 Dec 11.
    • NICE launches consultation on familial breast cancer guidelines.
    • Simon Leese.
    • PHG Foundation. 2013 Jan 15.
    • A classification model for BRCA2 DNA binding domain missense variants based on homology-directed repair activity.
    • Guidugli L, Pankratz VS, Singh N, Thompson J, Erding CA, Engel C, Schmutzler R, Domchek S, Nathanson K, Radice P, Singer C, Tonin PN, Lindor NM, Goldgar DE, Couch FJ.
    • Cancer Res. 2013 Jan 1;73(1):265-75. doi: 10.1158/0008-5472.CAN-12-2081. Epub 2012 Oct 29.
    • Analysis of 30 putative BRCA1 splicing mutations in hereditary breast and ovarian cancer families identifies exonic splice site mutations that escape in silico prediction.
    • Wappenschmidt B, Becker AA, Hauke J, Weber U, Engert S, Köhler J, Kast K, Arnold N, Rhiem K, Hahnen E, Meindl A, Schmutzler RK.
    • PLoS One. 2012;7(12):e50800. doi: 10.1371/journal.pone.0050800. Epub 2012 Dec 11.
    • Identification of a novel in-frame deletion in BRCA2 and analysis of variants of BRCA1/2 in Italian patients affected with hereditary breast and ovarian cancer.
    • Vietri MT, Molinari AM, Laura De Paola M, Cantile F, Fasano M, Cioffi M.
    • Clin Chem Lab Med. 2012 Dec;50(12):2171-80.
    • Identification of fifteen novel germline variants in the BRCA1 3'UTR reveals a variant in a breast cancer case that introduces a functional miR-103 target site.
    • Brewster BL, Rossiello F, French JD, Edwards SL, Wong M, Wronski A, Whiley P, Waddell N, Chen X, Bove B, Kconfab, Hopper JL, John EM, Andrulis I, Daly M, Volorio S, Bernard L, Peissel B, Manoukian S, Barile M, Pizzamiglio S, Verderio P, Spurdle AB, Radice P, Godwin AK, Southey MC, Brown MA, Peterlongo P.
    • Hum Mutat. 2012 Dec;33(12):1665-75. doi: 10.1002/humu.22159. Epub 2012 Aug 2.
    • To Improve Care for Your High Risk HBOC Patients, You Don’t Need the Supreme Court: It Is All in Your Hands — and In Your Files.
    • Laura Hercher.
    • The DNA Exchange. 2012 Nov 29.
    • A guide for functional analysis of BRCA1 variants of uncertain significance.
    • Millot GA, Carvalho MA, Caputo SM, Vreeswijk MP, Brown MA, Webb M, Rouleau E, Neuhausen SL, Hansen Tv, Galli A, Brandão RD, Blok MJ, Velkova A, Couch FJ, Monteiro AN; ENIGMA Consortium Functional Assay Working Group.
    • Hum Mutat. 2012 Nov;33(11):1526-37. doi: 10.1002/humu.22150. Epub 2012 Jul 16.
    • Multiple sequence variants of BRCA2 exon 7 alter splicing regulation.
    • Gaildrat P, Krieger S, Di Giacomo D, Abdat J, Révillion F, Caputo S, Vaur D, Jamard E, Bohers E, Ledemeney D, Peyrat JP, Houdayer C, Rouleau E, Lidereau R, Frébourg T, Hardouin A, Tosi M, Martins A.
    • J Med Genet. 2012 Oct;49(10):609-17. doi: 10.1136/jmedgenet-2012-100965. Epub 2012 Sep 7.
    • Functional evaluation of BRCA2 variants mapping to the PALB2-binding and C-terminal DNA-binding domains using a mouse ES cell-based assay.
    • Biswas K, Das R, Eggington JM, Qiao H, North SL, Stauffer S, Burkett SS, Martin BK, Southon E, Sizemore SC, Pruss D, Bowles KR, Roa BB, Hunter N, Tessarollo L, Wenstrup RJ, Byrd RA, Sharan SK.
    • Hum Mol Genet. 2012 Sep 15;21(18):3993-4006. doi: 10.1093/hmg/dds222. Epub 2012 Jun 7.
    • How genetic variant libraries effectively extend gene testing patents: implications for intellectual property and good clinical care.
    • McElligott S, Field RI, Bristol-Demeter M, Domchek SM, Asch DA.
    • J Clin Oncol. 2012 Aug 20;30(24):2943-5. Epub 2012 Jul 16.
    • A 24-color metaphase-based radiation assay discriminates heterozygous BRCA2 mutation carriers from controls by chromosomal radiosensitivity.
    • Becker AA, Graeser MK, Landwehr C, Hilger T, Baus W, Wappenschmidt B, Meindl A, Weber RG, Schmutzler RK.
    • Breast Cancer Res Treat. 2012 Aug;135(1):167-75. doi: 10.1007/s10549-012-2119-0. Epub 2012 Jun 23.
    • Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants.
    • Houdayer C, Caux-Moncoutier V, Krieger S, Barrois M, Bonnet F, Bourdon V, Bronner M, Buisson M, Coulet F, Gaildrat P, Lefol C, Léone M, Mazoyer S, Muller D, Remenieras A, Révillion F, Rouleau E, Sokolowska J, Vert JP, Lidereau R, Soubrier F, Sobol H, Sevenet N, Bressac-de Paillerets B, Hardouin A, Tosi M, Sinilnikova OM, Stoppa-Lyonnet D.
    • Hum Mutat. 2012 Aug;33(8):1228-38. doi: 10.1002/humu.22101. Epub 2012 May 11.
    • [Evaluation of variants of unknown significance in the BRCA2 gene].
    • Heczková M, Macháčková E, Jirsa M, Spičák J, Foretová L, Hucl T.
    • Klin Onkol. [2012 Aug;]25 Suppl:S87-95.
    • Review, [Article in Czech]
    • Collective evidence supports neutrality of BRCA1 V1687I, a novel sequence variant in the conserved THV motif of the first BRCT repeat.
    • Cortesi L, De Nicolo A, Medici V, Marino M, Turchetti D, Pradella LM, Rossi G, Parisini E, Federico M.
    • Breast Cancer Res Treat. 2012 Jul;134(1):435-41. doi: 10.1007/s10549-012-2052-2. Epub 2012 Apr 22.
    • Detection of exon skipping events in BRCA1 RNA using MLPA kit P002.
    • Brandão RD, Tserpelis D, Gómez García E, Blok MJ.
    • Mol Biol Rep. 2012 Jul;39(7):7429-33. doi: 10.1007/s11033-012-1575-2. Epub 2012 Feb 17.
    • Response to DNA damage of CHEK2 missense mutations in familial breast cancer.
    • Roeb W, Higgins J, King MC.
    • Hum Mol Genet. 2012 Jun 15;21(12):2738-44. doi: 10.1093/hmg/dds101. Epub 2012 Mar 13.
    • Comprehensive splicing functional analysis of DNA variants of the BRCA2 gene by hybrid minigenes.
    • Acedo A, Sanz DJ, Durán M, Infante M, Pérez-Cabornero L, Miner C, Velasco EA.
    • Breast Cancer Res. 2012 May 25;14(3):R87.
    • The BRCA1 alternative splicing variant Δ14-15 with an in-frame deletion of part of the regulatory serine-containing domain (SCD) impairs the DNA repair capacity in MCF-7 cells.
    • Sevcik J, Falk M, Kleiblova P, Lhota F, Stefancikova L, Janatova M, Weiterova L, Lukasova E, Kozubek S, Pohlreich P, Kleibl Z.
    • Cell Signal. 2012 May;24(5):1023-30. doi: 10.1016/j.cellsig.2011.12.023. Epub 2012 Jan 3.
    • Assessing the RNA effect of 26 DNA variants in the BRCA1 and BRCA2 genes.
    • Menéndez M, Castellsagué J, Mirete M, Pros E, Feliubadaló L, Osorio A, Calaf M, Tornero E, del Valle J, Fernández-Rodríguez J, Quiles F, Salinas M, Velasco A, Teulé A, Brunet J, Blanco I, Capellá G, Lázaro C.
    • Breast Cancer Res Treat. 2012 Apr;132(3):979-92. doi: 10.1007/s10549-011-1661-5. Epub 2011 Jul 7.
    • Characterization of BRCA1 and BRCA2 splicing variants: a collaborative report by ENIGMA consortium members.
    • Thomassen M, Blanco A, Montagna M, Hansen TV, Pedersen IS, Gutiérrez-Enríquez S, Menéndez M, Fachal L, Santamariña M, Steffensen AY, Jønson L, Agata S, Whiley P, Tognazzo S, Tornero E, Jensen UB, Balmaña J, Kruse TA, Goldgar DE, Lázaro C, Diez O, Spurdle AB, Vega A.
    • Breast Cancer Res Treat. 2012 Apr;132(3):1009-23. doi: 10.1007/s10549-011-1674-0. Epub 2011 Jul 19.
    • Prediction of BRCA2-association in hereditary breast carcinomas using array-CGH.
    • Joosse SA, Brandwijk KI, Devilee P, Wesseling J, Hogervorst FB, Verhoef S, Nederlof PM.
    • Breast Cancer Res Treat. 2012 Apr;132(2):379-89. doi: 10.1007/s10549-010-1016-7. Epub 2010 Jul 8.
    • Multimodel assessment of BRCA1 mutations in Taiwanese (ethnic Chinese) women with early-onset, bilateral or familial breast cancer.
    • Kuo WH, Lin PH, Huang AC, Chien YH, Liu TP, Lu YS, Bai LY, Sargeant AM, Lin CH, Cheng AL, Hsieh FJ, Hwu WL, Chang KJ.
    • J Hum Genet. 2012 Feb;57(2):130-8. doi: 10.1038/jhg.2011.142. Epub 2012 Jan 26.
    • ENIGMA--evidence-based network for the interpretation of germline mutant alleles: an international initiative to evaluate risk and clinical significance associated with sequence variation in BRCA1 and BRCA2 genes.
    • Spurdle AB, Healey S, Devereau A, Hogervorst FB, Monteiro AN, Nathanson KL, Radice P, Stoppa-Lyonnet D, Tavtigian S, Wappenschmidt B, Couch FJ, Goldgar DE; ENIGMA.
    • Hum Mutat. 2012 Jan;33(1):2-7. doi: 10.1002/humu.21628. Epub 2011 Nov 3.
    • A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS).
    • Lindor NM, Guidugli L, Wang X, Vallée MP, Monteiro AN, Tavtigian S, Goldgar DE, Couch FJ.
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