Chen W, Weghorst C M, Sabourin C L, Wang Y, Wang D, Bostwick D G, Stoner G D
Department of Pathology, School of Public Health, The Ohio State University, Columbus 43210, USA.
Carcinogenesis. 1996 Dec;17(12):2603-7. doi: 10.1093/carcin/17.12.2603.
The tumor suppressor gene p16/MTS1, located on chromosome 9p21, is a cell cycle regulatory gene which is frequently altered in human cancers. The role of this gene in prostate cancer is unknown. To determine the frequency of deletions and point mutations of p16/MTS1 in human prostate cancer, we examined 18 cancer and matched benign and hyperplastic tissue specimens. Deletions of p16/MTS1 were detected by semi-quantitative multiplex polymerase chain reaction in which a portion of exon 2 of the p16/MTS1 gene and a control marker, the glyceraldehyde 3-phosphate dehydrogenase gene, were amplified simultaneously. 'Cold' single-stranded conformational polymorphism (SSCP) analysis was performed to examine exons 1 and 2 of the p16/MTS1 gene for point mutations. Our data indicate no evidence for intragenic homozygous deletion in the prostate tumors. One prostate tumor and matched benign tissue showed mobility shifts. Direct DNA sequencing of the SSCP positive samples showed a G --> A transition in codon 140 which would result in an amino acid change from alanine to threonine. Our results indicate that deletions and point mutations in the p16/MTS1 gene are rare and do not play a major role in human prostate carcinogenesis.
位于9号染色体p21区域的肿瘤抑制基因p16/MTS1是一种细胞周期调控基因，在人类癌症中经常发生改变。该基因在前列腺癌中的作用尚不清楚。为了确定人类前列腺癌中p16/MTS1基因缺失和点突变的频率，我们检测了18例癌症组织以及配对的良性和增生性组织标本。通过半定量多重聚合酶链反应检测p16/MTS1基因的缺失，在该反应中，p16/MTS1基因的第2外显子部分和一个对照标记物甘油醛-3-磷酸脱氢酶基因同时被扩增。进行“冷”单链构象多态性（SSCP）分析以检测p16/MTS1基因第1和第2外显子的点突变。我们的数据表明在前列腺肿瘤中没有基因内纯合缺失的证据。一个前列腺肿瘤及其配对的良性组织显示出迁移率改变。对SSCP阳性样本进行直接DNA测序显示密码子140处发生了G→A转换，这将导致氨基酸从丙氨酸变为苏氨酸。我们的结果表明，p16/MTS1基因的缺失和点突变很少见，在人类前列腺癌发生过程中不发挥主要作用。
