Infrequent mutations and no methylation of CDKN2A (p16/MTS1) and CDKN2B (p15/MTS2) in hepatocellular carcinoma in Taiwan
Infrequent mutations and no methylation of CDKN2A (p16/MTS1) and CDKN2B (p15/MTS2) in hepatocellular carcinoma in Taiwan
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DOI：
10.1016/s0959-8049(98)00189-0
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发表时间：
1998-10-01
影响因子：
8.4
通讯作者：
Sheu, JC
中科院分区：
文献类型：
--
作者：
Lin, YW;Chen, CH;Sheu, JC
CDKN2A (p16(INK4A)/MTS1) 和 CDKN2B (p15(INK4B)/MTS2) 最近被证明是细胞周期蛋白 D/细胞周期蛋白依赖性激酶 4 复合物的有效抑制剂。这两个基因都是位于染色体 9p21 的假定肿瘤抑制基因的候选基因，并且在许多人类癌症中经常通过纯合缺失而失活。最近，另一种报道的失活途径涉及与人类癌症中 p16/MTS1 和 p15/MTS2 的 5' CpG 岛从头甲基化相关的转录丢失。我们通过聚合酶链式反应 (PCR) 扩增、序列分析和 Southern blot 检测了来自 30 名肝细胞癌 (HCC) 患者的总共 34 个肿瘤中这两个基因的缺失、突变和 DNA 甲基化。仅在 30 例病例中发现 1 例 (3%) 存在 P16/MTS1 外显子 1 纯合缺失。 30 例中有 7 例 (13%) 发现 p15 外显子 1 或外显子 2 纯合缺失。 p16 外显子 1 和 2 以及 p15 外显子 1 和 2 的自动测序分析未能证明这些样本中的 p16 或 p15 存在突变。通过 Southern 印迹，在任何原发性肿瘤中均未发现 p16 或 p15 的异常 5' CpG 岛高甲基化。这些数据表明 p16/MTS1 基因在 HCC 中的作用有限。然而，13% 的 HCC 中发现了 p15/MTS2 基因的缺失，并且可能与 HCC 的一个亚型有关。 (C) 1998 Elsevier Science Ltd. 保留所有权利。
CDKN2A (p16(INK4A)/MTS1) and CDKN2B (p15(INK4B)/MTS2) have recently been shown to be potent inhibitors of the cyclin D/cyclin-dependent kinase-4 complex. Both genes are candidates for the putative tumour suppressor genes located at chromosome 9p21 and are frequently inactivated in many human cancers through homozygous deletion. More recently, another reported pathway of inactivation involves loss of transcription associated with de novo methylation of the 5' CpG island of p16/MTS1 and p15/MTS2 in human cancers. We examined a total of 34 tumours from 30 hepatocellular carcinoma (HCC) patients for deletion, mutation and DNA methylation of these two genes by polymerase chain reaction (PCR) amplification, sequence analysis and Southern blot. Homozygous deletions of P16/MTS1 exon 1 were only identified in 1 of 30 cases (3%). Homozygous deletions of p15 exon 1 or exon 2 were found in 7 of 30 cases (13%). Automated sequencing analysis of p16 exon 1 and 2 and p15 exon 1 and 2 failed to demonstrate mutations in either p16 or p15 in any of these specimens. No aberrant 5' CpG island hypermethylation of p16 or p15 was found in any of the primary tumours by Southern blot. These data suggest that the p16/MTS1 gene has a limited role in HCC. However, deletions of the p15/MTS2 gene are found in 13% HCC and might be involved in a subset of HCC. (C) 1998 Elsevier Science Ltd. All rights reserved.