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

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作者：
Elisabeth Jarhelle
Hilde Monica Frostad Riise Stensland
Geir Åsmund Myge Hansen
Siri Skarsfjord
Christoffer Jonsrud
Monica Ingebrigtsen
Nina Strømsvik
Marijke Van Ghelue
机构：
[1] University Hospital of North Norway,Department of Medical Genetics, Division of Child and Adolescent Health
[2] University of Tromsø,Department of Clinical Medicine
[3] University Hospital of North Norway,Northern Norway Family Cancer Center, Department of Medical Genetics
[4] Western Norway University of Applied Sciences,Department of Health and Caring Sciences
来源：
Scientific Reports | / 9卷
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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.
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