摘要
背景:10%的胃癌与遗传因素相关。然而,对中国胃癌患者遗传易感基因的认识仍极为匮乏。本研究旨在确定中国人群中具有遗传高危因素的胃癌患者的遗传易感基因突变频率和突变谱。方法:纳入来自中国7家中心具有家族遗传性高危因素的40例胃癌患者,采用二代测序技术检测先证者与癌症遗传易感性相关的171个基因。对于发现存在已知致病或疑似致病突变的先证者,使用一代测序技术对先证者及其血亲进行突变位点的进一步验证。结果:40例患者中,有25%(10/40)先证者发现了涉及9个不同基因的10种已知致病或疑似致病突变,包括1例CDH1,1例MLH1,1例MSH2,1例CHEK2,1例BLM,1例EXT2,1例PALB2,1例ERCC2突变,2例SPINK1。此外,在27例患者中发现了129个意义未明的突变。结论:本研究显示,在具备遗传高危因素的中国胃癌患者中,每4例患者就有1例存在遗传易感基因的已知致病或疑似致病胚系突变。本研究结果进一步表明,中国胃癌患者可能具有独特的遗传背景。
Background Approximately 10%of patients with gastric cancer(GC)have a genetic predisposition toward the disease.However,there is scant knowledge regarding germline mutations in predisposing genes in the Chinese GC population.This study aimed to determine the spectrum and distribution of predisposing gene mutations among Chinese GC patients known to have hereditary high-risk factors for cancer.Methods A total of 40 GC patients from 40 families were recruited from seven medical institutions in China.Next-generation sequencing was performed on 171 genes associated with cancer predisposition.For probands carrying pathogenic/likely pathogenic germline variants,Sanger sequencing was applied to validate the variants in the probands as well as their relatives.Results According to sequencing results,25.0%(10/40)of the patients carried a combined total of 10 pathogenic or likely pathogenic germline variants involving nine different genes:CDH1(n=1),MLH1(n=1),MSH2(n=1),CHEK2(n=1),BLM(n=1),EXT2(n=1),PALB2(n=1),ERCC2(n=1),and SPINK1(n=2).In addition,129 variants of uncertain significance were identified in 27 patients.Conclusions This study indicates that approximately one in every four Chinese GC patients with hereditary high risk factors may harbor pathogenic/likely pathogenic germline alterations in cancer-susceptibility genes.The results further indicate a unique genetic background for GC among Chinese patients.
