BRCA1 and BRCA2 genetic testing-pitfalls and recommendations for managing variants of uncertain clinical significance

Annals of Oncology

Volumn 26, Issue 10, 2015, Pages 2057-2065

  Eccles, Encarna B ^a   Mitchell, G ^b,c   Monteiro, A N A ^d   Schmutzler, R ^e   Couch, F J ^f   Spurdle, A B ^g   Gomez Garcia E B ^h   Driessen, R ^a   Lindor, N M ^f   Blok, M J ^h   Moller, P ⁱ   de la Hoya, M ^j   Pal, T ^d   Domchek, S ^k   Nathanson, K ^k   Van Asperen, C ^l   Diez, O ^m   Rheim, K ^e   Stoppa Lyonnet, D ⁿ   Parsons, M ^g   Goldgar, D ^o   more..

^a SOUTHAMPTON GENERAL HOSPITAL   (United Kingdom)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^d H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^e University of Cologne   (Germany)

^f MAYO CLINIC   (United States)

^g QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^h MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

ⁱ OSLO UNIVERSITY HOSPITAL   (Norway)

^j HOSPITAL CLÍNICO SAN CARLOS   (Spain)

^k UNIVERSITY OF PENNSYLVANIA   (United States)

^l LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^m VALL D HEBRON UNIVERSITY HOSPITAL   (Spain)

ⁿ INSTITUT CURIE   (France)

^o UNIVERSITY OF UTAH   (United States)

more..

Author keywords

BRCA; Classification; Clinical utility; Variants of uncertain significance; VUS

Indexed keywords

BRCA1 PROTEIN; BRCA2 PROTEIN; BRCA1 PROTEIN, HUMAN; BRCA2 PROTEIN, HUMAN;

ADULT; ARTICLE; BREAST CANCER; CANCER RISK; CANCER SCREENING; CASE REPORT; CLINICAL PRACTICE; DISEASE CLASSIFICATION; FEMALE; GENE FREQUENCY; GENE MUTATION; GENETIC COUNSELING; GENETIC PREDISPOSITION; GENETIC SCREENING; GENETIC VARIABILITY; GENOTYPE; HUMAN; OVARY CANCER; PATHOGENICITY; PHENOTYPE; PRIORITY JOURNAL; SOMATIC MUTATION; TUMOR SUPPRESSOR GENE; BREAST NEOPLASMS; GENETIC VARIATION; GENETICS; MUTATION; OVARIAN NEOPLASMS; PRACTICE GUIDELINE; PROGNOSIS; RISK FACTOR; STANDARDS; STATISTICAL ANALYSIS;

BRCA1 PROTEIN; BRCA2 PROTEIN; BREAST NEOPLASMS; DATA INTERPRETATION, STATISTICAL; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; GENETIC VARIATION; HUMANS; MUTATION; OVARIAN NEOPLASMS; PRACTICE GUIDELINES AS TOPIC; PROGNOSIS; RISK FACTORS;

EID: 84943787980     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdv278     Document Type: Article

References (38)

1. Mavaddat N, Peock S, Frost D et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst 2013; 105: 812-822.
2. Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M. Genetic susceptibility to breast cancer. Mol Oncol 2010; 4: 174-191.
3. Risch HA, McLaughlin JR, Cole DE et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 2001; 68: 700-710.
4. Couch FJ, Hart SN, Sharma P et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol 2014; 33: 304-311.
5. Evans DGR, Barwell J, Eccles DM et al. The Angelina Jolie effect: how high celebrity profile can have a major impact on provision of cancer related services. Breast Cancer Res 2014; 16: 442-447.
6. James PA, Mitchell G, Bogwitz M, Lindeman GJ. The Angelina Jolie effect. Med J Aust 2013;199: 646.
7. Alsop K, Fereday S, Meldrum C et al. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol 2012; 30:2654-2663.
8. Tutt A, Robson M, Garber JE et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer:a proof-of-concept trial. Lancet 2010; 376: 235-244.
9. Schwartz MD, Lerman C, Brogan B et al. Impact of BRCA1/BRCA2 counseling and testing on newly diagnosed breast cancer patients. J Clin Oncol 2004; 22:1823-1829.
10. Vadaparampil ST, Scherr CL, Cragun D, Malo TL, Pal T. Pre-test genetic counseling services for hereditary breast and ovarian cancer delivered by nongenetics professionals in the state of Florida. Clin Genet 2014; 87: 473-477.
11. Pal T, Cragun D, Lewis C et al. A statewide survey of practitioners to assess knowledge and clinical practices regarding hereditary breast and ovarian cancer. Genet Test Mol Biomarkers 2013; 17: 367-375.
12. Wideroff L, Vadaparampil ST, Greene MH et al. Hereditary breast/ovarian and colorectal cancer genetics knowledge in a national sample of US physicians. J Med Genet 2005; 42: 749-755.
13. Chenevix-Trench G, Healey S, Lakhani S et al. Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance. Cancer Res 2006; 66: 2019-2027.
14. Eggington JM, Bowles KR, Moyes K et al. A comprehensive laboratory-based program for classification of variants of uncertain significance in hereditary cancer genes. Clin Genet 2014; 86: 229-237.
15. Lindor NM, Guidugli L, Wang X et al. A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS). Hum Mutat 2012; 33: 8-21.
16. Spurdle AB, Healey S, Devereau A et al. 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. Hum Mutat 2012; 33: 2-7.
17. Spurdle AB, Whiley PJ, Thompson B et al. BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk. J Med Genet 2012; 49: 525-532.
18. Plon SE, Eccles DM, Easton D et al. Sequence variant classification and reporting:recommendations for improving the interpretation of cancer susceptibility genetic test results. Hum Mutat 2008; 29: 1282-1291.
19. Moghadasi S, Hofland N, Wouts JN et al. Variants of uncertain significance in BRCA1 and BRCA2 assessment of in silico analysis and a proposal for communication in genetic counselling. J Med Genet 2013; 50: 74-79.
20. Goldgar DE, Easton DF, Deffenbaugh AM et al. Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. Am J Hum Genet 2004; 75: 535-544.
21. Walker LC, Whiley PJ, Couch FJ et al. Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence variants encoding missense substitutions:implications for prediction of pathogenicity. Hum Mutat 2010;31: E1484-E1505.
22. Millot GA, Carvalho MA, Caputo SM et al. A guide for functional analysis of BRCA1 variants of uncertain significance. Hum Mutat 2012; 33: 1526-1537.
23. Goldgar DE, Easton DF, Byrnes GB et al. Genetic evidence and integration of various data sources for classifying uncertain variants into a single model. Hum Mutat 2008; 29: 1265-1272.
24. Guidugli L, Carreira A, Caputo SM et al. Functional assays for analysis of variants of uncertain significance in BRCA2. Hum Mutat 2014; 35: 151-164.
25. Iversen ES Jr, Couch FJ, Goldgar DE, Tavtigian SV, Monteiro AN. A computational method to classify variants of uncertain significance using functional assay data with application to BRCA1. Cancer Epidemiol Biomarkers Prev 2011; 20:1078-1088.
26. Tavtigian SV, Greenblatt MS, Goldgar DE et al. Assessing pathogenicity: overview of results from the IARC Unclassified Genetic Variants Working Group. Hum Mutat 2008; 29: 1261-1264.
27. Anagnostopoulos T, Pertesi M, Konstantopoulou I et al. G1738R is a BRCA1 founder mutation in Greek breast/ovarian cancer patients: evaluation of its pathogenicity and inferences on its genealogical history. Breast Cancer Res Treat 2008; 110:377-385.
28. Newman B, Mu H, Butler LM et al. Frequency of breast cancer attributable to BRCA1 in a population-based series of American women. JAMA 1998; 279:915-921.
29. Blay P, Santamaria I, Pitiot AS et al. Mutational analysis of BRCA1 and BRCA2 in hereditary breast and ovarian cancer families from Asturias (Northern Spain). BMC Cancer 2013;13: 243.
30. Mirkovic N, Marti-Renom MA, Weber BL, Sali A, Monteiro AN. Structure-based assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition. Cancer Res 2004; 64: 3790-3797.
31. Tavtigian SV, Byrnes GB, Goldgar DE, Thomas A. Classification of rare missense substitutions, using risk surfaces, with genetic- and molecular-epidemiology applications. Hum Mutat 2008; 29: 1342-1354.
32. Spurdle AB, Couch FJ, Parsons MT et al. Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia. Breast Cancer Res 2014;16: 3419.
33. Guidugli L, Pankratz VS, Singh N et al. A classification model for BRCA2 DNA binding domain missense variants based on homology-directed repair activity. Cancer Res 2013; 73: 265-275.
34. Lindor NM, Goldgar DE, Tavtigian SV, Plon SE, Couch FJ. BRCA1/2 sequence variants of uncertain significance: a primer for providers to assist in discussions and in medical management. Oncologist 2013; 18: 518-524.
35. Petrucelli N, Lazebnik N, Huelsman KM, Lazebnik RS. Clinical interpretation and recommendations for patients with a variant of uncertain significance in BRCA1 or BRCA2: a survey of genetic counseling practice. Genet Test 2002; 6: 107-113.
36. Vos J, Gomez-Garcia E, Oosterwijk JC et al. Opening the psychological black box in genetic counseling. The psychological impact of DNA testing is predicted by the counselees' perception, the medical impact by the pathogenic or uninformative BRCA1/2-result. Psychooncology 2012; 21: 29-42.
37. Vos J, Otten W, van AC et al. The counsellees' view of an unclassified variant in BRCA1/2: recall, interpretation, and impact on life. Psychooncology 2008; 17:822-830.
38. Gomez-Garcia EB, Ambergen T, Blok MJ, van den Wijngaard A. Patients with an unclassified genetic variant in the BRCA1 or BRCA2 genes show different clinical features from those with a mutation. J Clin Oncol 2005;23: 2185-2190.