Open AccessGermline mutation landscape of Chinese patients with familial breast/ovarian cancer in a panel of 22 susceptibility genes
Author(s) -
Wang Jiayu,
Li Weiwei,
Shi Yujian,
Huang Yan,
Sun Tao,
Tang Lili,
Lu Qing,
Lei Qiumo,
Liao Ning,
Jin Feng,
Li Hui,
Huang Tao,
Qian Jun,
Pang Danmei,
Wang Shusen,
Fan Peizhi,
Wu Xinhong,
Lin Ying,
Qin Haiyan,
Xu Binghe
Publication year - 2019
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2093
Subject(s) - mutation , germline mutation , breast cancer , ovarian cancer , family history , gene , genetics , germline , cancer , mutation rate , genetic testing , medicine , biology , cancer research , oncology
Abstract Genetic testing for germline mutations in BRCA1/2 of patients with breast cancer (BC) is part of routine patient care. However, BRCA1/2 mutations account only for a fraction of familial BC. A custom panel of 22 gene sequencing was performed on each patient. Among the 481 female patients, 135 patients were detected to carry pathogenic (P)/likely pathogenic (LP) mutations (28.1%), which corresponded to 12 different cancer predisposition genes [14.6% (70/481) on BRCA1 gene, 5.0% (24/481) on BRCA2 gene, 8.5% (41/481) on non‐ BRCA1/2 genes]. Moreover, 24.7% (119/481) of patients had mutation of unknown significance (VUS) in these genes. The most common (8/481) pathogenic mutation is BRCA1 c.5470_5477del, while BRIP1 2392 C > T of patients was detected. All the mutations detected were mainly seen in the homologous recombinant repair pathway. Compared to BRCA2 mutation, BRCA1 mutation is higher in younger female patients ( P < 0.01). Some pathogenic mutations were detected in the patients’ familiy members without the past history of tumor and 92 novel mutations were detected (31 on BRCA including 2 P, 16 LP, 13 VUS; 61 on non‐ BRCA1/2 including 9 LP, 52 VUS). The detection rate of BRCA1/2 mutations was higher in patients with three or more cancer family members than those with one or two. However, the difference was not statistically different. The results suggest that multigene panel testing can increase mutation detection rate for high‐risk BC patients. Detailed family history can help to categorize new mutations.