Dong J T, Sipe T W, Hyytinen E R, Li C L, Heise C, McClintock D E, Grant C D, Chung L W, Frierson H F
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Oncogene. 1998 Oct 15;17(15):1979-82. doi: 10.1038/sj.onc.1202119.
Deletion of the q23-24 region of human chromosome 10 is one of the most frequent genetic alterations in prostate cancer, suggesting that inactivation of a tumor suppressor gene in this region is involved in the development or progression of this carcinoma. A candidate gene, PTEN/MMAC1, has been identified from this chromosomal region; mutations of this gene have been found in various advanced tumors and cell lines including those of prostate cancer. To further define the role of PTEN/MMAC1 in the development of prostate cancer and its spectrum of genetic alterations, we analysed 40 pT2 or pT3 prostate tumors for allelic loss, mutations, and homozygous deletions using PCR-based methods. Six tumors showed loss of heterozygosity for one of the ten markers analysed, while one tumor showed loss of two markers. None of the markers within PTEN/MMAC1 was lost. Direct sequencing of PCR amplified exons and intron/exon junctions of all 40 tumors revealed three sequence variants, one of which was a point mutation in exon 9, while the other two were polymorphisms. Using multiplex PCR, no homozygous deletions were detected in any of the neoplasms. Our results showing a low frequency of alterations of PTEN/MMAC1 in pT2 and pT3 prostate cancers suggest that this gene plays an insignificant role in the development of most low stage carcinomas of the prostate.
人类10号染色体q23 - 24区域的缺失是前列腺癌中最常见的基因改变之一，这表明该区域一个肿瘤抑制基因的失活与这种癌症的发生或发展有关。一个候选基因PTEN/MMAC1已从该染色体区域中被鉴定出来；在包括前列腺癌在内的各种晚期肿瘤和细胞系中都发现了该基因的突变。为了进一步明确PTEN/MMAC1在前列腺癌发生中的作用及其基因改变谱，我们使用基于PCR的方法分析了40例pT2或pT3前列腺肿瘤的等位基因缺失、突变和纯合缺失情况。6例肿瘤在所分析的10个标记物中的一个显示杂合性缺失，而1例肿瘤显示两个标记物缺失。PTEN/MMAC1内的标记物均未缺失。对所有40例肿瘤的PCR扩增外显子及内含子/外显子连接区进行直接测序，发现了3个序列变异，其中一个是外显子9中的点突变，另外两个是多态性。使用多重PCR，在任何肿瘤中均未检测到纯合缺失。我们的结果显示pT2和pT3前列腺癌中PTEN/MMAC1改变的频率较低，这表明该基因在大多数低分期前列腺癌的发生中起的作用不大。
