Patel U, Grundfest-Broniatowski S, Gupta M, Banerjee S
Department of Cancer Biology Research Institute, Cleveland Clinic Foundation, Ohio 44195.
Oncogene. 1994 Dec;9(12):3695-700.
The microsatellite instabilities at nine loci of chromosomes 2p, 8p, 10p and 11p and the nm23-H1 locus on 17q21.3 were studied in primary breast tumors. Alterations in the short interspersed tandem repeats in tumor DNA in the form of either larger allele, smaller allele or LOH were observed. Significantly, a high occurrence of alterations in microsatellite polymorphisms at the ANK1, D8S135 and LPL loci of chromosome 8p (46-54%), the D2S119 locus of chromosome 2p (56%), the D10S197 locus at chromosome 10p (88%), and the nm23-H1 locus of chromosome 17q21.3 (46%) were observed in breast tumors. These results provide the first evidence for genomic instabilities at 2p, 8p and 10p in primary ductal and lobular breast carcinomas. No correlation has been found between the stage of the tumor and microsatellite instability, suggesting that microsatellite instability is an early genetic event in breast carcinogenesis.
对原发性乳腺肿瘤中2号染色体短臂、8号染色体短臂、10号染色体短臂和11号染色体短臂的9个位点以及17号染色体长臂21.3区的nm23-H1位点的微卫星不稳定性进行了研究。观察到肿瘤DNA中短串联重复序列以较大等位基因、较小等位基因或杂合性缺失的形式发生改变。值得注意的是,在乳腺肿瘤中观察到8号染色体短臂的ANK1、D8S135和LPL位点(46%-54%)、2号染色体短臂的D2S119位点(56%)、10号染色体短臂的D10S197位点(88%)以及17号染色体长臂21.3区的nm23-H1位点(46%)的微卫星多态性改变发生率较高。这些结果为原发性导管癌和小叶癌中2号染色体短臂、8号染色体短臂和10号染色体短臂的基因组不稳定性提供了首个证据。未发现肿瘤分期与微卫星不稳定性之间存在相关性,这表明微卫星不稳定性是乳腺癌发生过程中的早期遗传事件。