ALLELOTYPE OF COLORECTAL CARCINOMAS
ALLELOTYPE OF COLORECTAL CARCINOMAS
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DOI：
10.1126/science.2565047
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发表时间：
1989-04-14
期刊：
影响因子：
56.9
通讯作者：
WHITE, R
中科院分区：
文献类型：
--
作者：
VOGELSTEIN, B;FEARON, ER;WHITE, R
为了研究常见成人肿瘤中等位基因丢失的程度和变化，对56对结直肠癌和邻近正常结肠粘膜标本中每个非近端着丝粒常染色体臂的多态性DNA标记进行了研究。这种分析被称为等位基因型，类似于核型。从该分析中得出三个主要结论：（i）等位基因缺失是非常常见的;测试的每个多态性标记的等位基因之一在至少一些肿瘤中丢失，并且一些肿瘤丢失了其亲本等位基因的一半以上。(ii)除了等位基因缺失，新的DNA片段不存在于正常组织中被确定在5个癌，这些新的片段包含重复序列的可变数目的串联重复类型。(iii)等位基因缺失百分比超过中位数的患者预后比其他患者差得多，尽管两组原发肿瘤的大小和分期非常相似。肿瘤等位基因型除了与肿瘤发生相关的遗传事件有关外，还可能为改善结直肠癌患者的预后评估提供一种分子工具。
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 polymporphic 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 additon 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.