Greenwald B D, Harpaz N, Yin J, Huang Y, Tong Y, Brown V L, McDaniel T, Newkirk C, Resau J H, Meltzer S J
Department of Medicine (GI Division), University of Maryland, Baltimore.
Cancer Res. 1992 Feb 1;52(3):741-5.
Allelic deletions of tumor suppressor genes have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancer. Three of the most frequently deleted chromosomal loci contain the tumor suppressor genes p53, retinoblastoma (Rb), and mcc/apc. In order to detect loss of heterozygosity (LOH) within these genes in dysplastic and cancerous ulcerative colitis, we used an application of the polymerase chain reaction. LOH affecting p53 was observed in 8 of 17 (47%) of heterozygous patients, while LOH of Rb and the mcc/apc locus was observed in 9 of 27 (33%) and 13 of 39 (33%) of heterozygotes, respectively. Among 35 patients heterozygous at 2 or more loci, LOH of p53, Rb, and/or mcc/apc was observed in 18 (51%). LOH was more common in left-sided neoplasms. These data suggest that allelic deletion of p53, Rb, mcc, and/or apc is involved in the pathogenesis and/or progression of at least a subset of colonic dysplasias and carcinomas occurring in the setting of ulcerative colitis.
在多种人类肿瘤中经常观察到肿瘤抑制基因的等位基因缺失。这些缺失被认为与人类癌症的发生有关。三个最常发生缺失的染色体位点包含肿瘤抑制基因p53、视网膜母细胞瘤（Rb）和mcc/apc。为了检测发育异常和癌变的溃疡性结肠炎中这些基因的杂合性缺失（LOH），我们应用了聚合酶链反应。在17名杂合患者中有8名（47%）观察到影响p53的LOH，而在27名杂合子中有9名（33%）观察到Rb的LOH，在39名杂合子中有13名（33%）观察到mcc/apc位点的LOH。在35名在2个或更多位点杂合的患者中，有18名（51%）观察到p53、Rb和/或mcc/apc的LOH。LOH在左侧肿瘤中更常见。这些数据表明，p53、Rb、mcc和/或apc的等位基因缺失参与了溃疡性结肠炎背景下至少一部分结肠发育异常和癌的发病机制和/或进展。
