Loss of constitutional heterozygosity in colon carcinoma from patients with familial polyposis coli-猫眼课题宝

家族性结肠息肉病患者结肠癌的体质杂合性缺失

DOI：

10.1038/331273a0

发表时间：

1988

期刊：

Nature

影响因子：

64.8

通讯作者：

中科院分区：

综合性期刊1区

文献类型：

作者：

M. Okamoto;M. Sasaki;K. Sugio;C. Sato;T. Iwama;T. Ikeuchi;A. Tonomura;T. Sasazuki;M. Miyaki

最近的研究表明，特定基因丢失在几种胚胎肿瘤1 -6和某些成人癌症7 -12中起着关键作用。在视网膜母细胞瘤中，隐性突变等位基因的半合性或纯合性导致正常基因产物的丢失2 -4，这似乎导致了该疾病的表现。家族性结肠息肉病（FPC）是一种常染色体显性遗传的人类疾病，以结肠和直肠的大量腺瘤性息肉和结肠癌的高发病率为特征。染色体组型分析未能检测到特定的缺失或易位。我们报告使用多态性DNA标记来寻找体细胞在特定位点的杂合性丢失。对25例FPC患者的38个肿瘤和19例患者的20个porad结肠癌的研究表明，22号染色体上的等位基因丢失频繁发生，5、6、12 q和15号染色体上也有一些丢失。FPC基因连锁的DNA探针C11 p11也检测到频繁的等位基因丢失在家族性和散发性结肠癌，但不是在良性腺瘤。这些结果表明，在家族性和散发性结肠癌的发展可能涉及一个以上的染色体位点。

Recent studies have suggested a critical role of specific gene loss in several embryonic tumours1–6 and certain adult cancers7–12. In retinoblastoma, hemizygosity or homozygosity of a recessive mutant allele results in the loss of normal gene product2–4, and this seems to cause the manifestation of the disorder. Familial polyposis coli (FPC) is a human autosomal dominant trait characterized by numerous adenomatous polyps of the colon and rectum, and a high incidence of colon carcinoma. Karyotype analyses have failed to detect specific deletion or translocation. We report the use of polymorphic DNA markers to look for the somatic loss of heterozygosity at specific loci. Investigation of 38 tumours from 25 FPC patients and 20 porad colon carcinomas from 19 patients, revealed frequent occurrence of allele loss on chromosome 22, with some additional losses on chromosomes 5, 6, 12q and 15. The FPC gene-linked DNA probe C11p11 also detected frequent allele loss in both familial and sporadic colon carcinomas but not in benign adenomas. These results suggest the possible involvement of more than one chromosomal locus in the development of familial and sporadic colon carcinomas.

Molecular genetic approach to human meningioma: loss of genes on chromosome 22.