Alterations of p14ARF and p16INK4a genes in salivary gland carcinomas.
Alterations of p14ARF and p16INK4a genes in salivary gland carcinomas.
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DOI：
10.3892/or.10.3.555
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发表时间：
2003-05
期刊：
影响因子：
4.2
通讯作者：
M. Nishimine;Mitsutoshi Nakamura;M. Kishi;M. Okamoto;K. Shimada;E. Ishida;T. Kirita;N. Konishi
中科院分区：
文献类型：
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作者：
M. Nishimine;Mitsutoshi Nakamura;M. Kishi;M. Okamoto;K. Shimada;E. Ishida;T. Kirita;N. Konishi
P14ARF和p16INK4a基因定位于9p21，据报道在各种人类肿瘤中经常发生基因改变。为了阐明它们在涎腺肿瘤发生中的地位，我们用甲基化特异性聚合酶链式反应、差异聚合酶链式反应和免疫组织化学方法分析了36例涎腺癌。P14ARF纯合子缺失(3例)或甲基化(7例)在10例(28%)SGC中检出，其中1例和3例分别显示p14ARF和p16INK4a基因的共缺失和共甲基化。共有5例(14%)SGCs显示p16INK4a纯合缺失(1例)或甲基化(4例)，除1例腺样囊性癌外，其余均为腺样囊性癌。免疫组织化学检测发现11例(31%)p14ARF和p16INK4a表达缺失，与基因状态有关。这些结果表明，p14ARF和p16INK4a基因的纯合缺失或启动子甲基化失活可能在涎腺恶性肿瘤的分子发病机制中起重要作用，并为表观遗传改变(如甲基化)与涎腺癌的发生有关提供了明确的证据。
The p14ARF and p16INK4a genes are localized to 9p21, where genetic alterations have been reported to be frequent in various human neoplasms. To elucidate their status in salivary gland tumorigenesis, we analyzed a series of 36 salivary gland carcinomas (SGCs) using methylation-specific PCR, differential PCR and immunohistochemistry. Homozygous deletion (3 cases) or methylation (7 cases) of p14ARF was detected in 10 (28%) SGCs, one and three showing co-deletion and co-methylation of both p14ARF and p16INK4a genes, respectively. A total of 5 (14%) SGCs demonstrated homozygous deletion (1 case) or methylation (4 cases) of p16INK4a, all but one being adenoid cystic carcinomas. Immunohistochemical study revealed loss of p14ARF and p16INK4a expression in 11 samples (31%), correlating with the gene status. These results indicate that inactivation of p14ARF and p16INK4a genes by either homozygous deletion or promoter hypermethylation may be important for the molecular pathogenesis of salivary malignant tumors, and provide clear evidence that epigenetic changes like methylation are related to salivary gland carcinogenesis.