Kámory Enikô, Tanyi Miklós, Kolacsek Orsolya, Olasz Judit, Tóth László, Damjanovich László, Csuka Orsolya
Department of Pathogenetics, National Institute of Oncology, Budapest, H-1122, Hungary.
Pathol Oncol Res. 2006;12(4):228-33. doi: 10.1007/BF02893417. Epub 2006 Dec 25.
The Bethesda guidelines may offer more useful criteria in patients' selection for germline mismatch repair gene mutation analysis than guidelines merely based on family background. An early onset double primary colorectal cancer patient with poor family history with MSI-H status was investigated for MLH1 promoter methylation, expression of the MLH1 and MSH2 gene by immunohistochemistry and mutations in the MLH1 and MSH2 genes. The index patient carried two germline alterations, the p.Val716Met in MLH1 and the c.2210+1G>C in MSH2 genes, and both tumors failed to express MLH1 and MSH2 proteins. After subsequent analysis of the whole family of the index patient, the p.Val716Met variant can be defined as a rare polymorphism with the possible contribution of pathogenicity to tumor formation and c.2210+1G>C as a true pathogenic mutation causing an out-of-frame deletion of exon 13.
与仅基于家族背景的指南相比，贝塞斯达指南在选择进行种系错配修复基因突变分析的患者时可能提供更有用的标准。对一名家族史不佳且为微卫星高度不稳定（MSI-H）状态的早发性双原发性结直肠癌患者进行了MLH1启动子甲基化、通过免疫组织化学检测MLH1和MSH2基因的表达以及MLH1和MSH2基因中的突变的研究。索引患者携带两个种系改变，即MLH1基因中的p.Val716Met和MSH2基因中的c.2210+1G>C，并且两个肿瘤均未表达MLH1和MSH2蛋白。在对索引患者的整个家族进行后续分析后，p.Val716Met变异可被定义为一种罕见的多态性，可能对肿瘤形成具有致病性贡献，而c.2210+1G>C则为真正的致病突变，导致外显子13的框外缺失。
