Li Jun, Han Sile, Zhang Cuiyun, Luo Yanlin, Wang Li, Wang Ping, Wang Yi, Xia Qingxin, Wang Xiaoyan, Wei Bing, Ma Jie, Li Hongle, Guo Yongjun
Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
Henan Key Laboratory of Molecular Pathology, Zhengzhou, China.
Front Oncol. 2021 May 11;11:655709. doi: 10.3389/fonc.2021.655709. eCollection 2021.
Predisposition of germline mutations ( ) increases the risk of breast and ovarian cancer in females, but the mutation prevalence and spectrum are highly ethnicity-specific with different recurrent mutations being reported in different populations. Hereby, we performed hybridization-based target sequencing of in 530 ovarian cancer patients from Henan, the central region of China, followed by haplotype analysis of six short tandem repeat (STR) markers in the patients with recurrent mutations to determine their founder effect. About 28.3% (150/530) of the OC patients in our cohort harbored ; of the 151 mutations, 117 in and 34 in , identified in this study, :c.5470_5477del, c.981_982del, and c.4065_4068del are the top three mutants, recurrently detected in eight, seven, and six independent patients respectively. Haplotype analysis identified a region of 0.6 MB genomic length covering highly conserved across all eight carriers of :c.5470_5477del, but not c.981_982del, suggesting a consequence of founder effect. Retrospective analysis in a subgroup of serous ovarian cancer patients revealed status was not associated with the progression-free survival (PFS); instead, an expression of Ki-67% ≥50% was associated with a shorter PFS ( = 0.041). In conclusion, patients with pathogenic or likely pathogenic account for 28.3% of the OC cases from Henan, and :c.5470_5477del, the most frequently detected mutation in Henan patients, is a founder mutation in the population.
种系突变（ ）的易感性增加了女性患乳腺癌和卵巢癌的风险，但突变的发生率和谱型具有高度种族特异性，不同人群中报道的复发性突变不同。在此，我们对来自中国中部地区河南的530例卵巢癌患者进行了基于杂交的 靶向测序，随后对复发性突变患者中的六个短串联重复序列（STR）标记进行单倍型分析，以确定其奠基者效应。我们队列中的约28.3%（150/530）卵巢癌患者携带 ；在本研究中鉴定出的151个突变中， 中有117个， 中有34个， :c.5470_5477del、c.981_982del和c.4065_4068del是前三个突变体，分别在8例、7例和6例独立患者中反复检测到。单倍型分析确定了一个0.6 MB基因组长度的区域，该区域在所有8例 :c.5470_5477del携带者中高度保守，但在c.981_982del携带者中不保守，提示这是奠基者效应的结果。对浆液性卵巢癌患者亚组的回顾性分析显示， 状态与无进展生存期（PFS）无关；相反，Ki-67%≥50%的表达与较短的PFS相关（ = 0.041）。总之，致病性或可能致病性 的患者占河南卵巢癌病例的28.3%， :c.5470_5477del是河南患者中最常检测到的突变，是该人群中的一个奠基者突变。
