北大p16甲基化前瞻性研究成果登Clin Cancer Res

　　

生物通报道，北京大学肿瘤医院病因学研究室邓大君教授等，与北京大学口腔医学院刘宏伟教授在癌症研究方面取得新的进展，相关成果文章Methylation of p16 CpG Island Associated with Malignant Progression of Oral Epithelial Dysplasia: A Prospective Cohort Study近期将发表于《Clinical Cancer Research》上。

 

口腔黏膜白斑是常见的癌前病变，伴有鳞状上皮异型增生者尤其容易发生癌变，重度异型增生部位需要手术切除。由于超过半数的轻度和中度黏膜异型增生不会发展成为癌症，学者们对其治疗方法存在争议。

 

据医药论坛报报道，邓大君等利用其在肿瘤表观遗传学研究方面的专利技术，开展前瞻性队列研究。他们对78例口腔黏膜轻度和中度异型增生患者平均随访4年，发现存在p16基因甲基化的患者44%进展为口腔癌，显著高于不存在p16基因甲基化的患者（17%进展为口腔癌）。这些结果表明，抑癌基因p16的甲基化失活能够用于早期诊断口腔黏膜异型增生是否癌变。

 

研究者利用使p16基因甲基化失活的方法，在年逾60岁的口腔黏膜异型增生患者中开展口腔癌早期诊断，其灵敏性和特异性均在76%以上，从而证实p16基因的异常甲基化失活，可用于对口腔癌的早期诊断。

 

目前，研究者正在筹划开发相关诊断试剂盒，并开展多中心临床试验，使更多口腔黏膜异型增生的患者能够尽早受益。

（生物通 小茜）

生物通推荐原文检索：

Methylation of p16 CpG Island Associated with Malignant Progression of Oral Epithelial Dysplasia: A Prospective Cohort Study

【Abstract】

Oral epithelial dysplasia (OED) is one of the common precancerous lesions among Chinese adults. Biomarker is not available for detection of malignant potential of OED till now. p16 is an important tumor suppressor gene, which is inactivated frequently by methylation of CpG island in early stage of carcinogenesis. The present cohort study is to investigate whether p16 methylation is correlated with malignant transformation of OED.

 

邓大君

学习工作经历

2003.7 ～ 今 , 北京大学临床肿瘤学院教授 

2001.4 ～ 2002.3 , Visiting Research Associate, University of Virginia Health Science Center 

1998.6 ～ 今 , 北京大学临床肿瘤学院病因室研究员、研究室主任 

1996.9 ～ 1996.11 , Guest Scientist, Federal Institute for Drugs and Medical Devices, Germany 

1994.9 ～ 1994.11 , Guest Scientist, Institute for Drugs, Federal Health Agency, Germany 

1993.7 ～ 1998.6 , 北京医科大学临床肿瘤学院病因室副研究员、研究室主任 

1992.8 ～ 1992.11 , Guest Scientist, Institute for Drugs, Federal Health Agency, Germany 

1983.9 ～ 1986.6 , 在中国医学科学院(肿瘤所)病理生理专业学习, 获硕士学位 

1978.10 ～ 1983.3 , 在江西医学院医疗系学习, 获学士学位 

 

研究课题

表观遗传学与癌变原理 

研究遗传和表观遗传变异在肿瘤发生发展中的作用，利用各种方法鉴定与肿瘤易感性和生物学行为相关的分子及其作用通路，并且用于肿瘤的预防和治疗。目前主要研究胃癌。 

 

代表论文

Microsatellite Instability and MLH1 Gene Inactivations in Sporadic Insulinomas: Clinical Implications.#,J Clin Endocr Metab,2009 

Methylation of p16 CpG Island Associated with Malignant Progression of Oral Epithelial Dysplasia: A Prospective Cohort Study*,Clin Cancer Res,2009 

Promoter methylation of p16 associated with Helicobacter pylori infection in precancerous gastric lesions: a population-based study,Intl J Cancer,2009,124(2):434-439 

Nucleosome Positions and Differential Methylation Status of Various Regions within the MLH1 CpG Island*,Chin J Cancer Res,2008,20(4):237-242 

Genetic polymorphisms of the E-cadherin promoter and risk of sporadic gastric carcinoma in Chinese populations*,Cancer Epidemiol Biomarkers Prev,2008,17(9):2402-2408 

Prevalence of A2143G mutation of H. pylori-23S rRNA in Chinese subjects with and without clarithromycin use history*,BMC Microb,2008,8:81 

Methylation of CpG islands of p16 associated with progression of primary gastric carcinomas quantitatively*,Laboratory Investigation,2006,86(6):591-598 

Genetic variants in cyclooxygenase-2, expression and risk of gastric cancer and its precursors in a Chinese population,Gastroenterol,2006,103(7):1975-1984 

Induction of gastric intraepithelial neoplasia of glandular stomach of Mogolian gerbils by Helicobacter pylori*,Chinese J Cancer Res,2005,17(3):190-192  

Formation of A2143G Mutation of 23S rRNA in progression of clarithromycin- resistance in Helicobacter pylori 26695*,Microb Drug Resist,2005,11(2):100-106 

Methylation of p16 CpG islands associated with malignant transformation of gastric dysplasia in a population-based study*,Clin Cancer Res,2004,10(15):5087-5093 

Short tandem repeat polymorphism in a novel esophageal cancer-related gene (ECRG2) implicates susceptibility to esophageal cancer in Chinese population,Intl J Cancer,2004,108(2):232-236 

Alterations of nitrate and nitrite content in saliva, serum, and urine in patients with salivary dysfunction,J Oral Pathol Med,2003,31:95-99 

Hypermethylation of metallothionein-3 CpG island in gastric carcinoma*,Carcinogenesis,2003,45(1):25-29 

Destruction of parotid glands in miniature pigs affects nitrate and nitrite levels in whole saliva, serum and urine*,J Dent Res,2003,82(2):101-105 

p16 hypermethylation during gastric carcinogenesis of wistar rats by MNNG*,Mutat Res,2003,535(1):73-78 

Silencing-Specific Methylation and single nucleotide polymorphism of hmlh1 promoter in gastric carcinomas*,World J Gastroenterology,2003,9(1):26-29