Germline mutation landscape of Chinese patients with familial breast/ovarian cancer in a panel of 22 susceptibility genes

• Published in: Cancer medicine (Malden, MA) MA), 2019-05, Vol.8 (5), p.2074-2084
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adult; Aged; Asian Continental Ancestry Group - genetics; BRCA1; BRCA1 protein; BRCA2; BRCA2 protein; Breast cancer; Breast Neoplasms - genetics; Clinical Cancer Research; familial breast cancer; Female; Genetic Predisposition to Disease; Genetic screening; Genetic Testing; Germ-Line Mutation; Health risk assessment; Humans; Middle Aged; multigenes; Mutation; novel mutation; Original Research; Ovarian cancer; Ovarian Neoplasms - genetics; Young Adult
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.2093

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