Peltomäki P
Department of Medical Genetics, University of Helsinki, Finland.
Environ Health Perspect. 1997 Jun;105 Suppl 4(Suppl 4):775-80. doi: 10.1289/ehp.105-1470030.
A new pathogenetic mechanism leading to cancer has been delineated in the past 3 years when human homologues of DNA mismatch repair (MMR) genes have been identified and shown to be involved in various types of cancer. Germline mutations of MMR genes cause susceptibility to a hereditary form of colon cancer, hereditary nonpolyposis colon cancer (HNPCC), which represents one of the most common syndromes associated with cancer predisposition in man. Tumors from HNPCC patients are hypermutable and show length variation at short tandem repeat sequences, a phenomenon referred to as microsatellite instability or replication errors. A similar abnormality is found in a proportion of sporadic tumors of the colorectum as well as a variety of other organs; acquired mutations in MMR genes or other endogenous or exogenous causes may underlie these cases. Genetic and biochemical characterization of the functions of normal and mutated MMR genes elucidates mechanisms of cancer development and provides tools for diagnostic applications.
在过去3年中，一种导致癌症的新发病机制已被阐明，在此期间，DNA错配修复（MMR）基因的人类同源物已被鉴定出来，并被证明与各种类型的癌症有关。MMR基因的种系突变会导致对一种遗传性结肠癌——遗传性非息肉病性结肠癌（HNPCC）易感，HNPCC是人类中与癌症易感性相关的最常见综合征之一。来自HNPCC患者的肿瘤具有高度易变性，并且在短串联重复序列处显示长度变异，这种现象被称为微卫星不稳定性或复制错误。在一部分散发性结直肠癌以及其他多种器官的肿瘤中也发现了类似的异常；MMR基因的获得性突变或其他内源性或外源性原因可能是这些病例的基础。对正常和突变MMR基因功能的遗传和生化特征分析阐明了癌症发展的机制，并为诊断应用提供了工具。
