P15^(INK4B)和P16^(INK4A)基因在鼻咽癌组织中异常甲基化  

Methylation patterns of P15^(INK4B) and P16^(INK4A) tumor suppressor genes in nasopharyngeal carcinoma tissues

作　　者：倪海峰[1] 莫颖禧[1] 周晓莹[1] 黄光武[1] 张哲[1] 

机构地区：[1]广西医科大学第一附属医院耳鼻咽喉头颈外科,南宁530021

出　　处：《中国药物与临床》2008年第6期440-442,共3页Chinese Remedies & Clinics

基　　金：国家自然科学基金资助项目(30660197)

摘　　要：目的通过检测P15INK4B和P16INK4A基因启动子区甲基化情况,分析其与鼻咽癌发生发展及临床病理特征关系,探讨其可能在鼻咽癌临床早期分子生物学诊断和治疗中的作用。方法运用甲基化特异性聚合酶链反应(PCR)对54例鼻咽癌组织和20例正常鼻咽上皮组织的P15INK4B和P16INK4A基因启动子区甲基化状态进行检测。结果鼻咽癌组织中P15INK4B和P16INK4A基因启动子区甲基化阳性率分别为22%(12/54)和46%(25/54),二者总检出率为48%(26/54),26例甲基化的癌组织同时出现二者甲基化为11例;而在正常鼻咽上皮组织中未检测到P15INK4B和P16INK4A基因启动子区甲基化。结论P15INK4B和P16INK4A基因启动子区甲基化与患者临床病理特征无明显相关关系,为鼻咽癌早期事件,有望成为早期分子生物学诊断的标志物,将来还可能作为去甲基化基因治疗的靶点。二者在鼻咽癌发生发展中可能存在协同作用。Objective To assess the promoter methylation patterns of P15^INK4B and P16^INK4A tumor suppressor genes in NPC as potential markers for early diagnosis and treatment targets. Methods The methylation-specific PCR （MSP） was used to detect methylation patterns of P15^INK4B and P16^INK4A tumor suppressor genes in 54 cases of NPC and 20 cases of normal nasopharyngeal epithelial tissues. Results Methylation expressions of P15^INK4B and P16^INK4A genes were found in 22.2%（12154） and 46.3% （25154） of NPC tissues, respectively. The overall rate of detection was 48.1% （26154）. Eleven of 26 cases showed hypermethylation in both P15^INK4B and P16^INK4A genes. No methylation of these genes was found in 20 cases of normal nasophatyngeal epithelial tissue. Conclusion The methylation patterns in P15^INK4B and P16^INK4A genes appear to be an early event in NPC that is independent of clinicopathologieal characteristics, and may show promises as biomarkers for earh＇ detection and as future targets for therapy of NPC. Both P15^INK4B and P16^INK4A genes may have synergistic effeets on development of the disease.

关 键 词：鼻咽肿瘤 P15^INK4B P16^INK4A甲基化 

分 类 号：R739.63[医药卫生—肿瘤]