Lynch syndrome (LS) is an inherited cancer susceptibility syndrome caused by germline mutations in a DNA mismatch repair (MMR) gene or in theEPCAMgene. LS is associated with an increased lifetime risk of colorectal cancer (CRC) and other malignancies. The screening algorithm for LS patient selection is based on the identification of CRC specimens that have MMR loss/high microsatellite instability (MSI-H) and are wild-type forBRAFV600. Here, we sought to clinically and molecularly characterize patients with these features. From 2017 to 2023, 841 CRC patients were evaluated for MSI andBRAFV600Emutation status, 100 of which showed MSI-H. Of these, 70 were wild-type forBRAFV600. Among these 70 patients, 30 were genetically tested for germline variants in hereditary cancer predisposition syndrome genes. This analysis showed that 19 of these 30 patients (63.3%) harbored a germline pathogenic or likely pathogenic variant in MMR genes, 2 (6.7%) harbored a variant of unknown significance (VUS) in MMR genes, 3 (10%) harbored a VUS in other cancer-related genes, and 6 (20%) were negative to genetic testing. These findings highlight the importance of personalized medicine for tailored genetic counseling, management, and surveillance of families with LS and other hereditary cancer syndromes.
林奇综合征（LS）是一种由DNA错配修复（MMR）基因或EPCAM基因的种系突变引起的遗传性癌症易感综合征。该综合征与结直肠癌（CRC）及其他恶性肿瘤的终生风险升高相关。LS患者筛查算法基于识别具有MMR缺失/高度微卫星不稳定性（MSI-H）且BRAF V600为野生型的CRC标本。本研究旨在从临床和分子层面对具有这些特征的患者进行表征。2017年至2023年间，共对841例CRC患者进行了MSI和BRAF V600E突变状态评估，其中100例显示MSI-H。在这100例患者中，70例为BRAF V600野生型。对这70例患者中的30例进行了遗传性癌症易感综合征基因的种系变异检测。分析显示：30例患者中19例（63.3%）携带MMR基因的致病性或可能致病性种系变异，2例（6.7%）携带MMR基因意义未明变异（VUS），3例（10%）携带其他癌症相关基因的VUS，6例（20%）遗传检测结果为阴性。这些发现凸显了个体化医疗对LS及其他遗传性癌症综合征家族进行精准遗传咨询、管理和监测的重要性。
肿瘤(癌症)患者之家