Wang S I, Parsons R, Ittmann M
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Clin Cancer Res. 1998 Mar;4(3):811-5.
A novel tumor suppressor gene, PTEN, which encodes a dual-specificity protein phosphatase, has recently been identified on chromosome 10q23. We have previously shown that both alleles of this gene are inactivated in three of four prostate cancer cell lines tested. To evaluate the role of inactivation of this gene in primary stage B prostate cancers, 60 cases were analyzed using Southern blotting with PTEN probes and microsatellites on 10q23. Eight of 60 cases had homozygous deletions by Southern blotting. In three of these cases, homozygous deletion was confirmed by apparent retention of heterozygosity at PTEN with loss of heterozygosity at telomeric and centromeric loci. In the remaining five cases, microsatellite analysis was consistent with homozygous deletion. Loss of heterozygosity at PTEN was found in only two cases both by microsatellite analysis and quantitative Southern blotting. No small mutations within PTEN exons were found in any tumors exhibiting alterations on 10q23. Thus, inactivation of the PTEN gene by homozygous deletion occurs in approximately 10-15% of primary stage B prostate carcinomas.
一种新的肿瘤抑制基因PTEN，它编码一种双特异性蛋白磷酸酶，最近在染色体10q23上被发现。我们之前已经表明，在检测的四种前列腺癌细胞系中的三种中，该基因的两个等位基因均失活。为了评估该基因失活在原发性B期前列腺癌中的作用，使用PTEN探针和10q23上的微卫星进行Southern印迹分析了60例病例。60例病例中有8例通过Southern印迹出现纯合缺失。在其中3例病例中，通过PTEN处杂合性的明显保留以及端粒和着丝粒位点杂合性的丧失证实了纯合缺失。在其余5例病例中，微卫星分析与纯合缺失一致。通过微卫星分析和定量Southern印迹仅在2例病例中发现PTEN处杂合性缺失。在任何显示10q23改变的肿瘤中均未发现PTEN外显子内的小突变。因此，纯合缺失导致的PTEN基因失活发生在大约10% - 15%的原发性B期前列腺癌中。
