Research Paper Volume 12, Issue 4 pp 3140—3155

Comparison of BRCA versus non-BRCA germline mutations and associated somatic mutation profiles in patients with unselected breast cancer

Bo Chen1, *, , Guochun Zhang1, *, , Xuerui Li1, *, , Chongyang Ren1, *, , Yulei Wang1,2, , Kai Li1, , Hsiaopei Mok1, , Li Cao1, , Lingzhu Wen1, , Minghan Jia1, , Cheukfai Li1, , Liping Guo1,3, , Guangnan Wei1,2, , Jiali Lin1,3, , Yingzi Li1,3, , Yuchen Zhang1,2, , Han Han-Zhang4, , Jing Liu4, , Analyn Lizaso4, , Ning Liao1, ,

  • 1 Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
  • 2 School of Medicine, South China University of Technology, Guangzhou, China
  • 3 The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
  • 4 Burning Rock Biotech, Guangzhou, China
* Equal contribution

Received: September 5, 2019       Accepted: January 20, 2020       Published: February 24, 2020
How to Cite

Copyright © 2020 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The data on the phenotypes associated with some rare germline mutations in Chinese breast cancer patients are limited. The difference in somatic mutation profiles in breast cancer patients with germline BRCA and non-BRCA mutations remains unexplored. We interrogated the germline and somatic mutational profile of 524 Chinese breast cancer patients with various stages unselected for predisposing factors using a panel consisting of 520 cancer-related genes including 62 cancer susceptibility genes. We divided the patients into three groups according to germline mutations: Germline-BRCA1/2, Germline-others (non-BRCA) and Others (non-carriers). A total of 58 patients (11.1%) carried 76 likely pathogenic or pathogenic (LP/P) germline variants in 15 cancer predisposition genes. Germline BRCA1/2 mutations were detected from 29 (5.53%) patients; with 11 (2.10%) BRCA1 carriers and 18 (3.44%) BRCA2 carriers. In addition, LP/P germline mutations were detected in other genes including MUTYH (n=4), PALB2 (n=4), ATM (n=3), BRIP1 (n=3), CDH1 (n=3), RAD51C (n=3), CHEK2 (n=2), FANCA (n=2), PMS2 (n=2), TP53 (n=2), FANCI (n=1), FANCL (n=1) and PTEN (n=1). At least one variant of uncertain significance (VUS) was identified in 490 (93.5%) patients. Young age (P=0.011), premenopausal status (P=0.013), and breast/ovarian cancer family history (P=0.001) were correlated with germline mutations. Germline-BRCA1/2 group was detected with more missense (P=0.02) and less copy-number amplification (P=0.04) than Germline-others group. Meanwhile, Germline-others group and Others group are very similar (P>0.05). The mutation rates of AKT1, CCND1, FGFR1, and PIK3CA were different among the three groups. By investigating all breast and ovarian cancer-related genes listed in the US genetic guidelines, we identified 15 cancer susceptibility genes frequently mutated in the germline of our population and must be included in cancer predisposition screening. Our study contributed a better understanding of the tumor characteristics of patients with LP/P germline mutations.


ACMG: American Society of Medical Genetics and Genomics; Cell-free DNA (cfDNA); ER: estrogen receptor; HER2: human epidermal growth factor receptor 2; LP/P: likely pathogenic or pathogenic; PR: progesterone receptor (PR); NGS: next-generation sequencing; VUS: variants of uncertain significance.