BRCA1 c.5470_5477del, a founder mutation in Chinese Han breast cancer patients. Issue 11 (22nd February 2020)

• Record Type: Journal Article
• Authors: Meng, Hua; Yao, Lu; Yuan, Hua; Xu, Ye; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao
• Is Part Of: International journal of cancer. Volume 146:Issue 11(2020)
• Page Start: 3044
• Page End: 3052
• Publication Date: 2020-02-22
• Subjects: breast cancer -- BRCA1 -- haplotype -- founder mutation -- Chinese; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.32877
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : The spectrum and frequency of BRCA1/2 pathogenic variants may be ethnicity‐specific. Whether high‐frequency founder mutations are present in Chinese women remains largely unknown. In the current study, germline pathogenic variants in the BRCA1/2 genes were determined in 9, 505 unselected Chinese Han breast cancer (BC) patients by next‐generation and/ or Sanger sequencing. Four hundred and seventy‐one (5.0%) BC patients carried BRCA1/2 pathogenic variants in this cohort. A total of 25 recurrent pathogenic variants (at least found in four unrelated patients) were identified in this cohort (8 BRCA1 and 17 BRCA2 recurrent pathogenic variants), 161 patients carried one of these recurrent pathogenic variants in this cohort of 9, 505 patients. All of these 25 recurrent pathogenic variants were further explored whether they had founder effect through haplotype analysis. The most common pathogenic variant, BRCA1 c.5470_5477del, was found in 30 BC patients from 29 unrelated families. Twenty‐seven of these 29 unrelated patients who carried this BRCA1 c.5470_5477del mutation shared an identical haplotype, indicating that BRCA1 c.5470_5477del was a founder mutation in the Chinese Han population. Furthermore, BRCA1 c.5470_5477del mutation carriers had a significantly worse survival than noncarriers (disease‐free survival, p = 0.049; overall survival, p = 0.029). Taken together, our data suggested that BRCA1 c.5470_5477del is a founder mutation in the Chinese Han population and BRCA1 c.5470_5477del mutation carriers have a poor survival. Abstract : What's new? Founder mutations in the BRCA1/2 genes are mostly defined in Caucasian populations while other ethnicities remain understudied. Here the authors studied a new gene variant in almost 10, 000 Chinese Han women with breast cancer. The BRCA1 c.5470_5477del variant was found in 0.3% of the women in the study, most of them sharing the same haplotype, suggesting that it functions as a new founder mutation in this ethnic population.