Okamoto M, Sasaki M, Sugio K, Sato C, Iwama T, Ikeuchi T, Tonomura A, Sasazuki T, Miyaki M
Department of Biochemistry, Tokyo Metropolitan Institute of Medical Science, Japan.
Nature. 1988 Jan 21;331(6153):273-7. doi: 10.1038/331273a0.
Recent studies have suggested a critical role of specific gene loss in several embryonic tumours and certain adult cancers. In retinoblastoma, hemizygosity or homozygosity of a recessive mutant allele results in the loss of normal gene product, 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 sporadic 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.
最近的研究表明，特定基因缺失在几种胚胎肿瘤和某些成人癌症中起着关键作用。在视网膜母细胞瘤中，隐性突变等位基因的半合子或纯合子会导致正常基因产物的缺失，这似乎会引发该疾病的表现。家族性结肠息肉病（FPC）是一种人类常染色体显性性状，其特征是结肠和直肠有大量腺瘤性息肉，且结肠癌发病率很高。核型分析未能检测到特定的缺失或易位。我们报告了使用多态性DNA标记来寻找特定基因座处杂合性的体细胞丢失。对来自25名FPC患者的38个肿瘤以及来自19名患者的20个散发性结肠癌进行的调查显示，22号染色体上频繁发生等位基因丢失，5号、6号、12q和15号染色体上也有一些额外的丢失。与FPC基因相关的DNA探针C11p11在家族性和散发性结肠癌中也检测到频繁的等位基因丢失，但在良性腺瘤中未检测到。这些结果表明，可能有多个染色体基因座参与了家族性和散发性结肠癌的发生。
