Vogelstein B, Fearon E R, Kern S E, Hamilton S R, Preisinger A C, Nakamura Y, White R
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Science. 1989 Apr 14;244(4901):207-11. doi: 10.1126/science.2565047.
To examine the extent and variation of allelic loss in a common adult tumor, polymorphic DNA markers were studied from every nonacrocentric autosomal arm in 56 paired colorectal carcinoma and adjacent normal colonic mucosa specimens. This analysis was termed an allelotype, in analogy with a karyotype. Three major conclusions were drawn from this analysis: (i) Allelic deletions were remarkably common; one of the alleles of each polymorphic marker tested was lost in at least some tumors, and some tumors lost more than half of their parental alleles. (ii) In addition to allelic deletions, new DNA fragments not present in normal tissue were identified in five carcinomas; these new fragments contained repeated sequences of the variable number of tandem repeat type. (iii) Patients with more than the median percentage of allelic deletions had a considerably worse prognosis than did the other patients, although the size and stage of the primary tumors were very similar in the two groups. In addition to its implications concerning the genetic events underlying tumorigenesis, tumor allelotype may provide a molecular tool for improved estimation of prognosis in patients with colorectal cancer.
为了研究常见成人肿瘤中等位基因缺失的程度和变异情况,我们对56对结直肠癌及相邻正常结肠黏膜标本的每一条非近端着丝粒常染色体臂上的多态性DNA标记进行了研究。这种分析类似于核型分析,被称为等位基因型分析。从该分析中得出了三个主要结论:(i)等位基因缺失非常常见;所检测的每个多态性标记的一个等位基因在至少一些肿瘤中丢失,并且一些肿瘤丢失了超过一半的亲本等位基因。(ii)除了等位基因缺失外,在5例癌组织中还鉴定出了正常组织中不存在的新DNA片段;这些新片段包含可变数目串联重复类型的重复序列。(iii)等位基因缺失百分比超过中位数的患者预后明显比其他患者差,尽管两组原发性肿瘤的大小和分期非常相似。除了其对肿瘤发生所涉及的遗传事件的影响外,肿瘤等位基因型可能为改善结直肠癌患者预后的评估提供一种分子工具。