该研究调查了55例头颈鳞状细胞癌（HNSCC）中p16(INK4A)，p14(ARF)和p15(INK4B)等多个肿瘤抑制基因的甲基化状态及其与临床病理参数的关系。结果显示，62%的肿瘤样本至少有一个基因发生异常甲基化，且p16(INK4A)甲基化最为常见，p14(ARF)甲基化与患者生存期缩短相关。
Abstract
4299
The aim of this study was to determine the association between methylation status of multiple tumor suppressor genes, p16(INK4A), p14(ARF), p15 (INK4B) in a HNSCCs and clinicopathological parameters. Aberrant methylation of p16(INK4A), is common gene silencing mechanism in HNSCC. However, aberrant methylation of p15 (INK4B) appears to be important and recently we demonstrated that TRβI is silencing by aberrant methylation. We investigated CpG island methylation of p16(INK4A), p14(ARF), p15 (INK4B) in a series of 55 primary HNSCCs and on healthy tissue to assess specificity of aberrant methylation. The samples were tested by methylation specific PCR (MSP) while gene expression was detected with real time RT-PC. Of the 55 HNSCCs examined, 34 (62%) tumors showed aberrant methylation at least on one of the genes tested and 15 % had two genes hypermethylated and 5% had three genes hypermethylated. Methylation frequencies varied with p16(INK4A) the most methylated and p14(ARF) the least. Aberrantly methylated genes were detected at early states (I and II) and at late stages (III and IV). No association between p16 (INK4A), p14 (ARF). p15 (INK4B) methylation and conventional clinicopathological parameters was observed. The presence of p14 (ARF) methylation was associated with shorter patient survival. In summary, we have identified a set of aberrant methylation signatures of the 9p21 locus tumor suppressor genes CDKN2A/p14(ARF)/CDKN2B that may be useful as tumor markers for the early identification of HNSCC patients.
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