Identifying sequence variants contributing to hereditary breast and ovarian cancer in BRCA1 and BRCA2 negative breast and ovarian cancer patients

被引：15

作者：

Jarhelle, Elisabeth ^{[1
,2
,3
]}

Stensland, Hilde Monica Frostad Riise ^{[1
,3
]}

Hansen, Geir Asmund Myge ^{[1
,3
]}

Skarsfjord, Siri ^{[1
]}

Jonsrud, Christoffer ^{[1
,3
]}

Ingebrigtsen, Monica ^{[1
]}

Stromsvik, Nina ^{[1
,3
,4
]}

Van Ghelue, Marijke ^{[1
,2
,3
]}

机构：

[1] Univ Hosp North Norway, Dept Med Genet, Div Child & Adolescent Hlth, Tromso, Norway

[2] Univ Tromso, Dept Clin Med, Tromso, Norway

[3] Univ Hosp North Norway, Dept Med Genet, Northern Norway Family Canc Ctr, Tromso, Norway

[4] Western Norway Univ Appl Sci, Dept Hlth & Caring Sci, Bergen, Norway

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

关键词：

GERMLINE MUTATIONS; ATAXIA-TELANGIECTASIA; SUSCEPTIBILITY GENE; ATM MUTATIONS; REPAIR; WOMEN; RISK; PREVALENCE; FREQUENCY; FANCM;

D O I：

10.1038/s41598-019-55515-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Families with breast and ovarian cancer are often tested for disease associated sequence variants in BRCA1 and BRCA2. Pathogenic sequence variants (PVs) in these two genes are known to increase breast and ovarian cancer risks in females. However, in most families no PVs are detected in these two genes. Currently, several studies have identified other genes involved in hereditary breast and ovarian cancer (HBOC). To identify genetic risk factors for breast and ovarian cancer in a Norwegian HBOC cohort, 101 breast and/or ovarian cancer patients negative for PVs and variants of unknown clinical significance (VUS) in BRCA1/2 were screened for PVs in 94 genes using next-generation sequencing. Sixteen genes were closely scrutinized. Nine different deleterious germline PVs/likely pathogenic variants (LPVs) were identified in seven genes in 12 patients: three in ATM, and one in CHEK2, ERCC5, FANCM, RAD51C, TP53 and WRN. Additionally, 32 different VUSs were identified and these require further characterization. For carriers of PV/LPV in many of these genes, there are no national clinical management programs in Norway. The diversity of genetic risk factors possibly involved in cancer development show the necessity for more knowledge to improve the clinical follow-up of this genetically diverse patient group.

引用

页数：12

共 84 条

[11] Genetic variation in the premature aging gene WRN:: A case-control study on breast cancer susceptibility [J].

Ding, Shian-ling ;

Yu, Jyh-Cherng ;

Chen, Shou-Tung ;

Hsu, Giu-Cheng ;

Shen, Chen-Yang .

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2007, 16 (02) :263-269

[12]

Dome J. S., TUMOR PREDISPOSITION

[13] Potentially pathogenic germline CHEK2 c.319+2T>A among multiple early-onset cancer families [J].

Dominguez-Valentin, Mev ;

Nakken, Sigve ;

Tubeuf, Helene ;

Vodak, Daniel ;

Ekstrom, Per Olaf ;

Nissen, Anke M. ;

Morak, Monika ;

Holinski-Feder, Elke ;

Martins, Alexandra ;

Moller, Pal ;

Hovig, Eivind .

FAMILIAL CANCER, 2018, 17 (01) :141-153

[14] Mutations in CHEK2 associated with prostate cancer risk [J].

Dong, XY ;

Wang, L ;

Taniguchi, K ;

Wang, XS ;

Cunningham, JM ;

McDonnell, SK ;

Qian, CP ;

Marks, AF ;

Slager, SL ;

Peterson, BJ ;

Smith, BI ;

Cheville, JC ;

Blute, ML ;

Jacobsen, SJ ;

Schaid, DJ ;

Tindall, DJ ;

Thibodeau, SN ;

Liu, WG .

AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 72 (02) :270-280

[15] Beyond BRCA: New hereditary breast cancer susceptibility genes [J].

Economopoulou, P. ;

Dimitriadis, G. ;

Psyrri, A. .

CANCER TREATMENT REVIEWS, 2015, 41 (01) :1-8

[16] Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2:: Analysis of 10,000 individuals [J].

Frank, TS ;

Deffenbaugh, AM ;

Reid, JE ;

Hulick, M ;

Ward, BE ;

Lingenfelter, B ;

Gumpper, KL ;

Scholl, T ;

Tavtigian, SV ;

Pruss, DR ;

Critchfield, GC .

JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (06) :1480-1490

[17] Rare variants in the ATM gene and risk of breast cancer [J].

Goldgar, David E. ;

Healey, Sue ;

Dowty, James G. ;

Da Silva, Leonard ;

Chen, Xiaoqing ;

Spurdle, Amanda B. ;

Terry, Mary Beth ;

Daly, Mary J. ;

Buys, Saundra M. ;

Southey, Melissa C. ;

Andrulis, Irene ;

John, Esther M. ;

Khanna, Kum Kum ;

Hopper, John L. ;

Oefner, Peter J. ;

Lakhani, Sunil ;

Chenevix-Trench, Georgia .

BREAST CANCER RESEARCH, 2011, 13 (04)

[18] Germline mutation in the RAD51B gene confers predisposition to breast cancer [J].

Golmard, Lisa ;

Caux-Moncoutier, Virginie ;

Davy, Gregoire ;

Al Ageeli, Essam ;

Poirot, Brigitte ;

Tirapo, Carole ;

Michaux, Dorothee ;

Barbaroux, Catherine ;

d'Enghien, Catherine Dubois ;

Nicolas, Andre ;

Castera, Laurent ;

Sastre-Garau, Xavier ;

Stern, Marc-Henri ;

Houdayer, Claude ;

Stoppa-Lyonnet, Dominique .

BMC CANCER, 2013, 13

[19] Rare and private variations in neural crest, apoptosis and sarcomere genes define the polygenic background of isolated Tetralogy of Fallot [J].

Grunert, Marcel ;

Dorn, Cornelia ;

Schueler, Markus ;

Dunkel, Ilona ;

Schlesinger, Jenny ;

Mebus, Siegrun ;

Alexi-Meskishvili, Vladimir ;

Perrot, Andreas ;

Wassilew, Katharina ;

Timmermann, Bernd ;

Hetzer, Roland ;

Berger, Felix ;

Sperling, Silke R. .

HUMAN MOLECULAR GENETICS, 2014, 23 (12) :3115-3128

[20] Extensive gene conversion at the PMS2 DNA mismatch repair locus [J].

Hayward, Bruce E. ;

De Vos, Michel ;

Valleley, Elizabeth M. A. ;

Charlton, Ruth S. ;

Taylor, Graham R. ;

Sheridan, Eamorm ;

Bonthron, David T. .

HUMAN MUTATION, 2007, 28 (05) :424-430

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