Carter S L, Negrini M, Baffa R, Gillum D R, Rosenberg A L, Schwartz G F, Croce C M
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Cancer Res. 1994 Dec 1;54(23):6270-4.
Studies of loss of heterozygosity (LOH) in breast tumor DNA suggest that several tumor suppressor genes participate in the pathogenesis of breast cancer. Although the short arm of chromosome 11 has been implicated in breast cancer development, no previous LOH studies have indicated the involvement of a suppressor gene on 11q in breast carcinoma. To this end, tumor samples and corresponding normal tissue were collected from 62 unselected patients with primary breast cancer, and the extracted DNA was analyzed by polymerase chain reaction using microsatellite markers on chromosome 11. We found that 39% of the tumors (22 of 57 informative cases) revealed allelic loss in the region 11q22-23, and this loss was independent of LOH found to occur on 11p15. Interestingly, more than 90% of the tumors showed concordant loss of alleles at both 11q and 17p. The marker D11S528, showing LOH in 39% of informative cases, had the highest frequency of LOH among the markers that were used. The data presented indicate that the common overlapping region of LOH is between the loci D11S35 and D11S29, suggesting that this area contains a tumor suppressor gene frequently lost in breast cancer.
对乳腺肿瘤DNA杂合性缺失(LOH)的研究表明,多个肿瘤抑制基因参与了乳腺癌的发病机制。尽管11号染色体短臂与乳腺癌发展有关,但之前的LOH研究均未表明11q上的一个抑制基因参与了乳腺癌的发生。为此,从62例未经挑选的原发性乳腺癌患者中收集了肿瘤样本及相应的正常组织,并使用11号染色体上的微卫星标记通过聚合酶链反应对提取的DNA进行分析。我们发现,39%的肿瘤(57例信息充分的病例中有22例)在11q22 - 23区域出现等位基因缺失,且这种缺失与11p15上发现的LOH无关。有趣的是,超过90%的肿瘤在11q和17p均出现了等位基因的一致性缺失。在39%的信息充分病例中显示出LOH的标记D11S528,在所使用的标记中具有最高的LOH频率。所呈现的数据表明,LOH的共同重叠区域在基因座D11S35和D11S29之间,这表明该区域包含一个在乳腺癌中经常缺失的肿瘤抑制基因。