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Cancer Med. 2019 May;8(5):2074-2084. doi: 10.1002/cam4.2093. Epub 2019 Apr 13.

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

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State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Top Gene Tech (Guangzhou) Co., Ltd., Guangzhou, China.
Department of Breast Surgery, Chinese People's Liberation Army, Beijing, China.
Department of Medical Oncology, Liaoning Cancer Hospital, Shenyang, China.
Department of Breast Surgery, Hunan Cancer Hospital, Changsha, China.
Department of Breast Surgery, West China Hospital of Sichuan university, Chengdu, China.
Department of Breast, The Third Hospital of Nanchang, Nanchang, China.
Department of Breast, Guangdong General Hospital, Guangzhou, China.
Department of Breast Surgery, The First Hospital of China Medical university, Shenyang, China.
Department of Breast Surgery, SiChuan Cancer Hospital Chengdu, Sichuan, China.
Department of Breast Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Breast Surgery, The First affiliated Hospital of bengbu medical college, Benghu, China.
Department of breast cancer oncology, Foshan Hospital of Sun Yat-Sen Unversity, Foshan, China.
Sun Yat-sen University, Guangzhou, China.
Department of Breast, Xiangya Hospital of Central South University, Changsha, China.
Department of Breast, Hubei Cancer Hospital, Benghu, China.
Department of Breast, the First affiliated Hospital of Sun Yat-Sen Unversity, Guangzhou, China.


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.


BRCA1 ; BRCA2 ; familial breast cancer; multigenes; novel mutation

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