Aaltonen L A, Peltomäki P
Department of Medical Genetics, University of Helsinki, Finland.
Anticancer Res. 1994 Jul-Aug;14(4B):1657-60.
Hereditary nonpolyposis colorectal cancer (HNPCC) (Lynch syndrome) accounts for a small proportion of the total colorectal cancer burden, yet represents the most common form of dominantly inherited colon cancer. Until recently, the diagnosis has been based on family history of colorectal and other intra-abdominal cancers. This has been problematic since chance clustering of such tumors cannot be excluded. On the other hand, not every HNPCC patients shows a dramatic family history of cancer. Genetic mapping of a locus for HNPCC to chromosome 2p and the observation that HNPCC tumors show instability of short tandem repeat sequences (replication errors, RER) rapidly led to the cloning of the predisposing gene, human MSH2 (hMSH2). Mutations of hMSH2 have been demonstrated to segregate in large HNPCC families with the cancer phenotype, thus providing convincing evidence that the gene indeed, when mutated, predisposes its carriers to colorectal and other intra-abdominal tumors. Localization of a second locus for HNPCC to chromosome 3p and the subsequent cloning of another predisposing gene, human MLH1 (hMLH1) give hope that a great majority of families can soon be diagnosed by molecular genetic methods.
遗传性非息肉病性结直肠癌（HNPCC）（林奇综合征）在结直肠癌总负担中所占比例较小，但却是显性遗传结肠癌最常见的形式。直到最近，诊断一直基于结直肠癌和其他腹腔内癌症的家族史。由于不能排除此类肿瘤的偶然聚集，这一直存在问题。另一方面，并非每个HNPCC患者都有明显的癌症家族史。将HNPCC的一个基因座定位到2号染色体短臂，以及观察到HNPCC肿瘤显示短串联重复序列不稳定（复制错误，RER），很快导致了易感基因人错配修复蛋白2（hMSH2）的克隆。已证明hMSH2突变在具有癌症表型的大型HNPCC家族中呈分离状态，从而提供了令人信服的证据，即该基因在发生突变时确实会使其携带者易患结直肠癌和其他腹腔内肿瘤。将HNPCC的第二个基因座定位到3号染色体短臂，随后克隆了另一个易感基因人错配修复蛋白1（hMLH1），这让人们希望绝大多数家族很快就能通过分子遗传学方法进行诊断。
