Chromosome 5 allele loss in familial and sporadic colorectal adenomas.
Chromosome 5 allele loss in familial and sporadic colorectal adenomas.
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DOI：
10.1038/bjc.1989.72
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发表时间：
1989-03
影响因子：
8.8
通讯作者：
Jass JR
中科院分区：
文献类型：
--
作者：
Rees M;Leigh SE;Delhanty JD;Jass JR
从家族性和散发性结直肠肿瘤中提取的DNA与体质DNA进行比较，使用一系列高变位点特异性探针来评估在恶性肿瘤转化过程中等位基因丢失的程度。在23%的癌症样本中观察到5号染色体等位基因丢失，这与之前其他人的发现一致。然而，我们首次在3例腺瘤患者的5号染色体上发现了D5S43位点的缺失，其中2例患有癌前状态的大肠腺瘤性息肉病（APC）。这些结果提示在良性腺瘤中发生了涉及5号染色体的显著遗传改变。1号染色体（D1S7和D1S8位点）和7号染色体（D7S21和D7S22位点）的探针在腺瘤样本中未发现明显改变。在癌症中没有观察到7号染色体上等位基因的完全丢失，但在三个标本中发现了一个亲本等位基因的强度降低，其中一个已知具有该染色体的多个拷贝。使用1号染色体探针的结果表明，D1S7或D1S8位点的缺失在结直肠癌发生中并不常见。APC患者腺瘤中5号染色体等位基因的缺失为Knudson的假说提供了支持证据。
DNA extracted from familial and sporadic colorectal neoplasms was compared with constitutional DNA using a range of hypervariable locus specific probes to assess the extent of allele loss during conversion to malignancy. Chromosome 5 allele loss was observed in 23% of carcinoma samples, as previously found by others. However, we have been able to show for the first time loss of the D5S43 locus on chromosome 5 in adenomas from three patients, two of whom had the precancerous condition adenomatous polyposis coli (APC). These results suggest significant genetic changes involving chromosome 5 are occurring in benign adenomas. Probes for chromosome 1 (loci D1S7 and D1S8) and for chromosome 7 (loci D7S21 and D7S22) revealed no notable alterations in the adenoma samples. Complete loss of alleles for loci on chromosome 7 was not observed in carcinomas but reduced intensity of one parental allele was found in three specimens one of which was known to have multiple copies of this chromosome. Results using probes for chromosome 1 suggest that deletion of the D1S7 or D1S8 loci is not a common event in colorectal carcinogenesis. Loss of chromosome 5 alleles in adenomas from APC patients provides evidence in support of Knudson's hypothesis.