Inactivation of the p16 gene by hypermethylation and loss of heterozygosity in adenocarcinoma of the lung
Inactivation of the p16 gene by hypermethylation and loss of heterozygosity in adenocarcinoma of the lung
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DOI：
10.1111/j.1440-1827.2004.01655.x
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发表时间：
2004-07-01
影响因子：
2.2
通讯作者：
Inai, K
中科院分区：
文献类型：
--
作者：
Awaya, H;Takeshima, Y;Inai, K
我们检测了48例肺腺癌组织中p16、p15和p14基因启动子异常甲基化和9p21-22杂合性缺失(LOH)。P16、p15、p14基因甲基化频率分别为25.0%、22.9%、18.8%。染色体9p21-22的杂合性缺失频率为60.9%。高甲基化和杂合性缺失导致p16基因二次失活的频率为21.7%。P16基因二次失活后蛋白表达缺失，与肿瘤大小、肿瘤分级和Ki-67标记指数显著相关。P16基因的高甲基化与p15和p14基因的高甲基化没有明显的相关性，这两个基因都靠近p16基因位点，这表明这些基因的高甲基化发生了选择性。结论：p16基因高甲基化和LOH双等位基因失活可能导致p16基因表达缺失，在肺腺癌的发生发展中起重要作用。因此，控制和监测p16基因的高甲基化状态可能对肺腺癌的治疗和早期诊断有一定的帮助。
We investigated the aberrant promoter hypermethylation of p16, p15 and p14 genes and loss of heterozygosity (LOH) at 9p21-22 in 48 cases of adenocarcinoma of the lung. The frequencies of hypermethylation of genes were as follows: p16, 25.0%; p15, 22.9%; and p14, 18.8%. The frequency of LOH at chromosome 9p21-22 was 60.9%. The frequency of two-hit inactivation of the p16 gene by hypermethylation and LOH was 21.7%. Two-hit inactivation of the p16 gene showed loss of protein expression and was significantly correlated with tumor size, tumor grade and the Ki-67 labeling index. Hypermethylation of the p16 gene was not significantly correlated with hypermethylation of the p15 and p14 genes, both of which are close to the p16 gene locus, suggesting that hypermethylation of these genes occurs selectivity. In conclusion, biallelic inactivation of the p16 gene by hypermethylation and LOH might cause loss of p16 expression and play an important role in the development of adenocarcinoma of the lung. Therefore, controlling and monitoring for hypermethylation of the p16 gene may be partially useful for treatment and early diagnosis of adenocarcinoma of the lung.