Title: Assessing pathogenicity: overview of results from the IARC Unclassified Genetic Variants Working Group
Abstract: Human MutationVolume 29, Issue 11 p. 1261-1264 OverviewFree Access Assessing pathogenicity: overview of results from the IARC Unclassified Genetic Variants Working Group† Sean V. Tavtigian, Corresponding Author Sean V. Tavtigian [email protected] International Agency for Research on Cancer (IARC); Lyon, FranceInternational Agency for Research on Cancer; Lyon 69372, FranceSearch for more papers by this authorMarc S. Greenblatt, Marc S. Greenblatt Vermont Cancer Center and Department of Medicine, University of Vermont; Burlington, VermontSearch for more papers by this authorDavid E. Goldgar, David E. Goldgar Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UtahSearch for more papers by this authorPaolo Boffetta, Paolo Boffetta International Agency for Research on Cancer (IARC); Lyon, FranceSearch for more papers by this authorfor the IARC Unclassified Genetic Variants Working Group, for the IARC Unclassified Genetic Variants Working Group The members of the Working Group are listed in the Appendix.Search for more papers by this author Sean V. Tavtigian, Corresponding Author Sean V. Tavtigian [email protected] International Agency for Research on Cancer (IARC); Lyon, FranceInternational Agency for Research on Cancer; Lyon 69372, FranceSearch for more papers by this authorMarc S. Greenblatt, Marc S. Greenblatt Vermont Cancer Center and Department of Medicine, University of Vermont; Burlington, VermontSearch for more papers by this authorDavid E. Goldgar, David E. Goldgar Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UtahSearch for more papers by this authorPaolo Boffetta, Paolo Boffetta International Agency for Research on Cancer (IARC); Lyon, FranceSearch for more papers by this authorfor the IARC Unclassified Genetic Variants Working Group, for the IARC Unclassified Genetic Variants Working Group The members of the Working Group are listed in the Appendix.Search for more papers by this author First published: 24 October 2008 https://doi.org/10.1002/humu.20903Citations: 70 † For the Mutation Pathogenicity Special Issue AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL REFERENCES Castilla LH, Couch FJ, Erdos MR, Hoskins KF, Calzone K, Garber JE, Boyd J, Lubin MB, Deshano ML, Brody LC, Collins FS, Weber BL. 1994. Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer. Nat Genet 8: 387– 391. Chenevix-Trench G, Healey S, Lakhani S, Waring P, Cummings M, Brinkworth R, Deffenbaugh AM, Burbidge LA, Pruss D, Judkins T, Scholl T, Bekessy A, Marsh A, Lovelock P, Wong M, Tesoriero A, Renard H, Southey M, Hopper JL, Yannoukakos K, Brown M, Easton D, Tavtigian SV, Goldgar D, Spurdle AB. 2006. Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance. Cancer Res 66: 2019– 2027. Couch FJ, Rasmussen L, Hofstra R, Monteiro AANM, Greenblatt MS, de Wind N, IARC Unclassified Genetic Variants Working Group. 2008. Assessment of functional effects of unclassified genetic variants. Hum Mutat 29: 1314– 1326. Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE. 2007. A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet 81: 873– 883. Frank TS, Deffenbaugh AM, Reid JE, Hulick M, Ward BE, Lingenfelter B, Gumpper KL, Scholl T, Tavtigian SV, Pruss DR, Critchfield GC. 2002. Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol 20: 1480– 1490. Goldgar DE, Easton DF, Deffenbaugh AM, Monteiro AN, Tavtigian SV, Couch FJ. 2004. Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. Am J Hum Genet 75: 535– 544. Goldgar DE, Easton DF, Byrnes GB, Spurdle AB, Iversen ES, Greenblatt MS; IARC Unclassified Genetic Variants Working Group. 2008. Integration of various data sources for classifying uncertain variants into a single model. Hum Mutat 29: 1265– 1272. Greenblatt MS, Brody LC, Foulkes W, Genuardi M, Hofstra R, Plon S, Sijmons RH, Sinilnikova OM, Spurdle AB. 2008. Locus-specific databases and recommendations to strengthen their contribution to the classification of variants in cancer susceptibility genes. Hum Mutat 29: 1273– 1281. Hofstra RW, Spurdle AB, Eccles D, Foulkes WD, de Wind N, Hoogerbrugge N, Hogervorst FBL; IARC Unclassified Genetic Variants Working Group. 2008. Tumor characteristics as an analytic tool for classifying genetic variants of uncertain clinical significance. Hum Mutat 29: 1292– 1303. Krasnov K, Tzetis M, Cheng J, Guggino W, Cutting GR. 2008. Functional studies of rare missense mutations in CFTR facilitate interpretation of genotype-phenotype relationships. Hum Mutat 29: 1364– 1372. Kryukov GV, Pennacchio LA, Sunyaev SR. 2007. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am J Hum Genet 80: 727– 739. Lynch HT, Boland CR, Rodriguez-Bigas MA, Amos C, Lynch JF, Lynch PM. 2007. Who should be sent for genetic testing in hereditary colorectal cancer syndromes? J Clin Oncol 25: 3534– 3542. Ollila S, Dermadi Bebek D, Jiricny J; Nystrom M. 2008. Mechanisms of pathogenicity in human MSH2 missense mutants. Hum Mutat 29: 1355– 1363. Ou J, Niessen RC, Vonk J, Westers H, Hofstra RMW, Sijmons RH. 2008. A database to support the interpretation of human mismatch repair gene variants. Hum Mutat 29: 1337– 1341. Plon SE, Eccles DM, Easton DF, Foulkes W, Genuardi M, Greenblatt MS, Hogervorst FBL, Hoogerbrugge N, Spurdle AB, Tavtigian S; IARC Unclassified Genetic Variants Working Group. 2008. Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. Hum Mutat 29: 1282– 1291. Spurdle AB, Couch FJ, Hogervorst FBL, Radice P, Sinilnikova OM; IARC Unclassified Genetic Variants Working Group. 2008a. Prediction and assessment of splicing alterations. Hum Mutat 29: 1304– 1313. Spurdle AB, Lakhani SR, Healey S, Parry S, Da Silva LM, Brinkworth R, Hopper JL, Brown MA, Babikyan D, Chenevix-Trench G, Tavtigian SV, Goldgar DE. 2008b. Clinical classification of BRCA1 and BRCA2 DNA sequence variants: the value of cytokeratin profiles and evolutionary analysis—a report from the kConFab Investigators. J Clin Oncol 26: 1657– 1663. Tavtigian SV, Deffenbaugh AM, Yin L, Judkins T, Scholl T, Samollow PB, de Silva D, Zharkikh A, Thomas A. 2006. Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral. J Med Genet 43: 295– 305. Tavtigian S, Byrnes GB, Goldgar DE, Thomas A. 2008a. Classification of rare missense substitutions, using risk surfaces, with genetic- and molecular-epidemiology applications. Hum Mutat 29: 1342– 1354. Tavtigian SV, Greenblatt MS, Lesueur F, Byrnes GB; IARC Unclassified Genetic Variants Working Group. 2008b. In silico analysis of missense substitutions using sequence-alignment based methods. Hum Mutat 29: 1327– 1336. Citing Literature Volume29, Issue11Special Issue: Special Issue: Assessing Mutation Pathogenicity in Cancer Susceptibility GenesNovember 2008Pages 1261-1264 ReferencesRelatedInformation