Aberrant promoter hypermethylation of p16 and MGMT genes in oral squamous cell carcinomas and the surrounding normal mucosa
Aberrant promoter hypermethylation of p16 and MGMT genes in oral squamous cell carcinomas and the surrounding normal mucosa
复制标题
DOI：
10.1007/s00432-006-0122-8
复制
发表时间：
2006-11-01
影响因子：
3.6
通讯作者：
Shibata, Toshiyuki
中科院分区：
文献类型：
--
作者：
Kato, Keizo;Hara, Akira;Shibata, Toshiyuki
目的研究口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）的发生与多种基因改变的关系。最近的研究表明，在几种类型的癌症中，肿瘤抑制基因（包括p16和MGMT）的启动子超甲基化发挥作用。本研究的目的是检测p16和MGMT基因在口腔癌和癌旁正常粘膜中的高甲基化状态。方法应用甲基化特异性PCR（MSP）检测51例口腔鳞癌、2例疣状癌和2例原位癌组织中p16和MGMT基因启动子区的甲基化状态。另外，在51例OSCC中，22例还检查了癌周围的正常粘膜。结果p16和MGMT基因启动子区异常甲基化分别在50.9%（28/55）和56.4%（31/55）的口腔癌组织中检出。在22例口腔鳞癌组织中，p16和MGMT基因启动子甲基化阳性率分别为72.73%（16/22）和68.18%（15/22）。在癌旁正常口腔黏膜中，p16和MGMT基因启动子区甲基化率分别为27.27%（6/22）和40.91%（9/22）。因此，p16和MGMT基因启动子的高甲基化是口腔癌发生的一个重要的，可能是早期事件。
Purpose Several genetic alterations have been reported to contribute to the development of oral squamous cell carcinoma (OSCC. Recent studies have shown roles of promoter hypermethylation of tumor suppressor genes, including p16 and MGMT, in several types of cancers. The purpose of this study is to examine the hypermethylation status of p16 and MGMT genes in both oral cancers and normal mucosa, surrounding the cancers. Methods Promoter hypermethylation status of p16 and MGMT genes were examined by the methylation-specific PCR (MSP) in OSCC (n=51), verrucous carcinoma (n=2), and carcinoma in situ (n=2) tissues. Moreover, normal mucosa surrounding the cancers were also examined in 22 cases out of the 51 OSCCs. As a normal control, oral mucosa from healthy volunteers (n=18) was used.Results Aberrant promoter hypermethylation of p16 and MGMT genes was detected in 50.9% (28 of 55) and 56.4% (31 of 55) of the total malignant cases, respectively. As for the 22 OSCC cases, in which paired cancerous tissues and the surrounding normal mucosa were examined simultaneously, promoter hypemethylation of p16 and MGMT genes was confirmed in 72.73% (16 of 22) and 68.18% (15 of 22), respectively. In contrast, as for the surrounding normal mucosa, promoter hypermethylation of p16 and MGMT genes was recognized in 27.27% (6 of 22) cases and 40.91% (9 of 22), respectively.Conclusions Hypermethylation of both p16 and MGMT genes was frequently detected in not only OSCC tissues, but also the surrounding normal mucosa around the cancerous tissues. Thus promoter hypermethylation of p16 and MGMT genes are an important, probably early event in oral carcinogenesis.