Wieland I, Ammermüller T, Böhm M, Totzeck B, Rajewsky M F
Institute of Cell Biology (Cancer Research), University of Essen Medical School, Germany.
Oncol Res. 1996;8(1):1-5.
Microsatellite alterations observed in tumor specimens may reflect genomic instability due to defective mismatch repair genes. To investigate whether this occurs in human nonsmall cell lung carcinomas we have analyzed microsatellite instability at 5 marker loci and loss of heterozygosity (LOH) at the hMLH1 locus on chromosome 3p21 using the polymerase chain reaction. Of a total of 49 nonsmall cell lung carcinomas examined, 43% (13 of 30 informative cases) showed LOH at 3p21 and 29% (14 of 49) exhibited microsatellite instability at one or multiple loci. LOH of the mismatch repair gene hMLH1 at 3p21 occurred in 82% (9 of 11 informative cases) of the tumors with microsatellite instability. This suggests that defects in the mismatch repair gene hMLH1 at 3p21 may be involved in microsatellite instability and tumorigenesis of a subset of nonsmall cell lung carcinomas. However, in those nonsmall cell lung carcinomas without microsatellite instability LOH at 3p21 probably involved another tumor suppressor gene(s) in this chromosomal region.
在肿瘤标本中观察到的微卫星改变可能反映了由于错配修复基因缺陷导致的基因组不稳定。为了研究这种情况是否发生在人类非小细胞肺癌中，我们使用聚合酶链反应分析了5个标记位点的微卫星不稳定性以及3号染色体p21区域hMLH1位点的杂合性缺失（LOH）。在总共49例接受检查的非小细胞肺癌中，43%（30例信息丰富的病例中有13例）在3p21处显示出杂合性缺失，29%（49例中有14例）在一个或多个位点表现出微卫星不稳定。在具有微卫星不稳定的肿瘤中，82%（11例信息丰富的病例中有9例）在3p21处发生错配修复基因hMLH1的杂合性缺失。这表明3p21处错配修复基因hMLH1的缺陷可能与一部分非小细胞肺癌的微卫星不稳定和肿瘤发生有关。然而，在那些没有微卫星不稳定的非小细胞肺癌中，3p21处的杂合性缺失可能涉及该染色体区域的另一个肿瘤抑制基因。
