Open AccessMultigene panel analysis identified germline mutations of DNA repair genes in breast and ovarian cancer
Author(s) -
Hirotsu Yosuke,
Nakagomi Hiroshi,
Sakamoto Ikuko,
Amemiya Kenji,
Oyama Toshio,
Mochizuki Hitoshi,
Omata Masao
Publication year - 2015
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.157
Subject(s) - germline , gene , breast cancer , genetics , ovarian cancer , biology , dna , germline mutation , dna repair , mutation , cancer research , cancer
Approximately 5–10% of all breast and/or ovarian cancer cases are considered as inherited. BRCA 1 and BRCA 2 tumor suppressor genes account for a high penetrance of hereditary cases, but familial cases without mutations in these genes can also occur. Despite their low penetrance, other hereditary cancer‐related genes are known to be associated with breast and ovarian cancer risk. However, the extent to which these genes prevail in breast and ovarian cancer remains to be elucidated. To estimate the frequency of mutations in these predisposition genes, we analyzed the germline mutations of 25 hereditary cancer‐related genes in 155 patients using targeted next‐generation sequencing. These subjects included 11 BRCA 1/2 mutation‐positive cases and 144 negative cases. Of these, three patients (1.9%) had pathogenic mutations in ATM , MRE 11A , or MSH 6 , all of which have a central role in DNA repair and the mismatch repair pathway. The MSH 6 splice‐site mutation ( IVS 6+1G>T) was predicted to be pathogenic, as demonstrated by in vitro and immunohistochemical analyses. These results suggested deficiencies in cellular DNA repair functions result in the development of breast and ovarian cancer.