Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
J Hum Genet. 2010 Jan;55(1):37-41. doi: 10.1038/jhg.2009.119. Epub 2009 Nov 13.
Mutations in mismatch repair genes lead to Lynch Syndrome, the most common form of inherited colorectal cancer. In this report, we describe a novel complex germline mutation c.[1601_1661+92dup; 1591_1611del] of the mismatch repair gene, MSH2. This mutation, which segregates with the disease phenotype, was discovered in a Lynch syndrome kindred that also shows a history of the Muir-Torre syndrome. Interestingly, several tumors from this family displayed microsatellite instability, a hallmark of Lynch syndrome tumors but no consistent, concomitant loss of MSH2 protein expression. In addition, a subset of tumors showed neither prototypical feature of microsatellite instability nor immunohistochemistry deficiency, highlighting the importance of a detailed molecular analysis of rare genetic alterations. This mutation and the atypical clinical manifestations observed underscore the genetic complexity underlying Lynch syndrome, and the importance of comprehensive molecular screening in the diagnosis and early detection of colorectal and other associated cancers.
错配修复基因的突变导致林奇综合征，这是最常见的遗传性结直肠癌形式。在本报告中，我们描述了一种新型的错配修复基因 MSH2 的胚系复合突变 c.[1601_1661+92dup; 1591_1611del]。该突变与疾病表型分离，在一个也显示 Muir-Torre 综合征病史的林奇综合征家族中发现。有趣的是，该家族的一些肿瘤显示微卫星不稳定性，这是林奇综合征肿瘤的标志，但没有一致的、伴随的 MSH2 蛋白表达缺失。此外，一部分肿瘤既没有微卫星不稳定性的典型特征，也没有免疫组织化学缺陷，突出了对罕见遗传改变进行详细分子分析的重要性。该突变和观察到的非典型临床表现强调了林奇综合征遗传复杂性的重要性，以及综合分子筛查在结直肠癌和其他相关癌症的诊断和早期检测中的重要性。
