BRCA1 c.5470_5477del, a founder mutation in Chinese Han breast cancer patients
BRCA1 c.5470_5477del, a founder mutation in Chinese Han breast cancer patients
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BRCA1 c.5470_5477del，中国汉族乳腺癌患者的创始人突变
DOI：
10.1002/ijc.32877
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发表时间：
2020-02-22
影响因子：
6.4
通讯作者：
Xie, Yuntao
中科院分区：
文献类型：
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作者：
Meng, Hua;Yao, Lu;Xie, Yuntao
BRCA1/2致病变异体的谱和频率可能因种族而异。在很大程度上，中国女性是否存在创始人高频突变仍是个未知数。本研究通过下一代和/或Sanger测序对9505例中国汉族乳腺癌(BC)患者进行了BRCA1/2基因种系致病变异的检测。471例(5.0%)BC患者携带BRCA1/2致病变异体。在这个队列中总共发现了25个复发致病变异(至少在4个无关患者中发现)(8个BRCA1和17个BRCA2复发致病变异)，在这个9505名患者队列中，161名患者携带这些复发致病变异之一。通过单倍型分析进一步探讨这25个复发致病变异体是否具有创始人效应。最常见的致病突变是BRCA1 c.5470_5477del，它发生在29个无血缘关系的家系的30例BC患者中。在29例携带BRCA1 c.5470_5477del突变的无关患者中，27例患者具有相同的单倍型，表明BRCA1 c.5470_5477del是中国汉族人群中的一种方正突变。此外，BRCA1c.54705477del突变携带者的存活率明显低于非携带者(无病存活率，p=0.049；总存活率，p=0.029)。综上所述，我们的数据提示BRCA1 c.5470_5477del是中国汉族人群中的一种方正突变，BRCA1 c.5470_5477del突变携带者的存活率较低。
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.