Introduction: Deleterious heterozygous mutation of the MLH1 gene is an important cause of Lynch syndrome (LS), an autosomal dominant cancer caused by functional defects in the DNA mismatch repair (MMR) complex. Case Report: The proband was a 35-year-old patient with confirmed colorectal cancer (CRC). Immunohistochemical (IHC) staining revealed the absence of MLH1 and PMS2 expression in the colorectal tissue specimens of the patient. Genetic counselling and tumor gene testing were performed using next-generation sequencing technology. The genetic tumor verification report showed the deletion of 4 bases in exon 12 of the tested MLH1 gene and a transcoding mutation. To our knowledge, this germline splice site mutation of MLH1 has not been reported before. The proband accepted several therapeutic regimens including PD-1 inhibitor and ultimately died of multiple organ failure. Conclusion: Nonsense mutations and frameshift mutations of MMR genes are the most common causes of LS. Common mutations include those in MSH2, MLH1, MSH6, and PMS2. We report a mutation of MLH1 that has never been reported before. We recommend that patients with a history of colon or rectal cancer receive universal MMR or MSI testing and checkpoint inhibitor therapy for the first-line treatment of deficient MMR CRC.
Oncol Res Treat

中文翻译：

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MLH1 外显子 12 基因缺失导致 Lynch 综合征：病例报告

简介： MLH1 基因的有害杂合突变是林奇综合征 (LS) 的重要原因，林奇综合征 (LS) 是一种由 DNA 错配修复 (MMR) 复合体的功能缺陷引起的常染色体显性遗传癌症。案例报告：先证者是一名 35 岁的确诊结直肠癌 (CRC) 患者。免疫组织化学 (IHC) 染色显示患者的结直肠组织标本中不存在 MLH1 和 PMS2 表达。使用新一代测序技术进行遗传咨询和肿瘤基因检测。基因肿瘤鉴定报告显示受试MLH1基因外显子12缺失4个碱基，存在转码突变。据我们所知，MLH1 的这种种系剪接位点突变以前没有报道过。先证者接受了包括PD-1抑制剂在内的多种治疗方案，最终死于多器官衰竭。结论：MMR 基因的无义突变和移码突变是 LS 的最常见原因。常见的突变包括 MSH2、MLH1、MSH6 和 PMS2 中的突变。我们报告了以前从未报道过的 MLH1 突变。我们建议有结肠癌或直肠癌病史的患者接受通用 MMR 或 MSI 检测和检查点抑制剂治疗，用于 MMR 缺陷型 CRC 的一线治疗。
肿瘤资源治疗