Pantaleo Antonino, Forte Giovanna, Cariola Filomena, Valentini Anna Maria, Fasano Candida, Sanese Paola, Grossi Valentina, Buonadonna Antonia Lucia, De Marco Katia, Lepore Signorile Martina, Guglielmi Anna Filomena, Manghisi Andrea, Gigante Gianluigi, Armentano Raffaele, Disciglio Vittoria, Simone Cristiano
Medical Genetics, National Institute of Gastroenterology-IRCCS "Saverio de Bellis" Research Hospital, Castellana Grotte, 70013 Bari, Italy.
Department of Pathology, National Institute of Gastroenterology-IRCCS "Saverio de Bellis" Research Hospital, Castellana Grotte, 70013 Bari, Italy.
Cancers (Basel). 2023 Oct 19;15(20):5061. doi: 10.3390/cancers15205061.
Lynch syndrome (LS) is an inherited cancer susceptibility syndrome caused by germline mutations in a DNA mismatch repair (MMR) gene or in the gene. 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 for . Here, we sought to clinically and molecularly characterize patients with these features. From 2017 to 2023, 841 CRC patients were evaluated for MSI and mutation status, 100 of which showed MSI-H. Of these, 70 were wild-type for . 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）是一种遗传性癌症易感性综合征，由DNA错配修复（MMR）基因或 基因中的种系突变引起。LS与结直肠癌（CRC）和其他恶性肿瘤的终生风险增加有关。LS患者选择的筛查算法基于对具有MMR缺失/高微卫星不稳定性（MSI-H）且 为野生型的CRC标本的鉴定。在此，我们试图从临床和分子角度对具有这些特征的患者进行表征。2017年至2023年，对841例CRC患者进行了MSI和 突变状态评估，其中100例显示为MSI-H。在这些患者中，70例 的检测结果为野生型。在这70例患者中，30例对遗传性癌症易感综合征基因中的种系变异进行了基因检测。该分析表明，这30例患者中有19例（63.3%）在MMR基因中携带种系致病或可能致病的变异，2例（6.7%）在MMR基因中携带意义未明的变异（VUS），3例（10%）在其他癌症相关基因中携带VUS，6例（20%）基因检测结果为阴性。这些发现凸显了个性化医疗对于为LS和其他遗传性癌症综合征家庭提供量身定制的遗传咨询、管理和监测的重要性。
