Lynch syndrome is a cancer-predisposing syndrome inherited in an autosomal-dominant manner, wherein colon cancer and endometrial cancer develop frequently in the family, it results from a loss-of-function mutation in one of four different genes (MLH1, MSH2, MSH6, and PMS2) encoding mismatch repair proteins. Being located immediately upstream of the MSH2 gene, EPCAM abnormalities can affect MSH2 and cause Lynch syndrome. Mismatch repair proteins are involved in repairing of incorrect pairing (point mutations and deletion/insertion of simple repetitive sequences, so-called microsatellites) that can arise during DNA replication. MSH2 forms heterodimers with MSH6 or MSH3 (MutSα, MutSβ, respectively) and is involved in mismatch-pair recognition and initiation of repair. MLH1 forms a complex with PMS2, and functions as an endonuclease. If the mismatch repair system is thoroughly working, genome integrity is maintained completely. Lynch syndrome is a state of mismatch repair deficiency due to a monoallelic abnormality of any mismatch repair genes. The phenotype indicating the mismatch repair deficiency can be frequently shown as a microsatellite instability in tumors. Children with germline biallelic mismatch repair gene abnormalities were reported to develop conditions such as gastrointestinal polyposis, colorectal cancer, brain cancer, leukemia, etc., and so on, demonstrating the need to respond with new concepts in genetic counseling. In promoting cancer genome medicine in a new era, such as by utilizing immune checkpoints, it is important to understand the genetic and genomic molecular background, including the status of mismatch repair deficiency.

中文翻译：

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Lynch综合征所涉及的错配修复系统的遗传和基因组基础。

Lynch综合征是一种以常染色体显性遗传的癌症易感综合征，其中结肠癌和子宫内膜癌在家族中频繁发生，它是由四个不同基因（MLH1，MSH2，MSH6中之一）的功能丧失突变导致的和PMS2）编码错配修复蛋白。EPCAM异常位于MSH2基因的上游，可影响MSH2并引起Lynch综合征。错配修复蛋白参与DNA复制过程中可能出现的错误配对（点突变和简单重复序列的缺失/插入，所谓的微卫星）的修复。MSH2与MSH6或MSH3形成异二聚体（分别为MutSα，MutSβ），并参与错配对识别和修复启动。MLH1与PMS2形成复合物，并起核酸内切酶的作用。如果错配修复系统正常运行，则基因组完整性将得到完全维护。林奇综合征是由于任何错配修复基因的单等位基因异常而导致的错配修复缺陷状态。指示错配修复缺陷的表型可以经常显示为肿瘤中的微卫星不稳定性。据报道，具有种系双等位基因错配修复基因异常的儿童发展为胃肠道息肉病，结肠直肠癌，脑癌，白血病等疾病，这表明需要在遗传咨询中采用新概念应对。在新时代推广癌症基因组医学中，例如通过利用免疫检查点，重要的是了解遗传和基因组分子背景，包括错配修复缺陷的状态。