回族 Lynch 综合征一家系错配修复基因表达及突变情况分析

摘要

Objective To investigate the expression and mutations of DNA mismatch repair ( MMR) of Lynch syn-drome in the members of a Chinese Hui family.Methods The propositus was male, 37 years old, the forth generation, Hui nationality, had rectal poorly differentiated adenocarcinoma.There were six generations existing ( Hui nationality), and a total of 14 patients with colorectal cancer were found including 7 living cases.The peripheral blood and tumor tissue DNA was collected from 6 cases of patients and 5 healthy controls.The microsatellite instability ( MSI ) was detected through DNA sequencing, the expression of MMR protein was measured using immunohistochemistry, and MMR gene muta-tions was detected by PCR amplification.Results The MSI detection of tumor tissues in the family members demonstrated MSI-H.The immunohistochemistry showed that MLH1 protein was negative.Two new missense mutation sites ( c.264G>T and c.265G>T) in the first exon of MLH1 gene were found in 6 patients and 1 normal individual, and c.264G>T mu-tation led to early termination of MLH1 protein translation on this site.Conclusion There is MLH1 mutation in Hui family with Lynch syndrome, that is the missense muntation site c.264G>T in the first exon of MLH1 gene.%目的：分析回族Lynch综合征一家系错配修复基因（ MMR）表达及突变情况，探讨回族Lynch综合征的基因特点。方法先证者男性，37岁，第4代，回族，直肠低分化腺癌。本家系现存6代（均为回族），共有结直肠癌患者14例，在世7例。提取本家系中6例患者及5例正常人外周血及肿瘤组织DNA。采用DNA测序检测肿瘤细胞DNA微卫星不稳定性（MSI），采用免疫组化法检测肿瘤细胞MMR表达，采用PCR技术检测MMR基因突变情况。结果该家系结直肠癌患者肿瘤组织MSI检测均表现为高度微卫星不稳定性（ MSI-H）；肿瘤组织MMR家族中MLH1表达均为阴性；MLH1基因第一外显子存在2个新的错义突变位点c．264G＞T、c．265G＞T，其中c．265G＞T突变导致MLH1基因蛋白质翻译在该位点提前终止。结论回族Lynch综合征家系存在MLH1基因突变，即存在第一外显子错义突变位点c．265G＞T。