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High frequency of p16(INK4A) gene alterations in hepatocellular carcinoma (1999)_香港中文大学

香港中文大学 辅仁网/2017-06-27

High frequency of p16(INK4A) gene alterations in hepatocellular carcinoma
Publication in refereed journal


香港中文大学研究人员 ( 现职)
刘允怡教授 (外科学系)
梁惠棠教授 (肿瘤学系)
赖宝山教授 (外科学系)
廖传佳教授 (外科学系)
罗国炜教授 (病理解剖及细胞学系)


全文


引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/142WOS source URL

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摘要The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) is an important component of the cell cycle and inactivation of the gene has been found in a variety of human cancers. In order to investigate the role of p16 gene in the tumorigenesis of hepatocellular carcinoma (HCC), 48 cases of HCC were analysed for p16 alterations by: methylation-specific PCR (MSP) to determine the methylation status of the p16 promoter region; comparative multiplex PCR to detect homozygous deletion; PCR-SSCP and DNA sequencing analysis to identify mutation of the p16 gene. We found high frequency of hypermethylation of the 5' CpG island of the p16 gene in 30 of 48 cases (62.5%) of HCC tumors. Moreover, homozygous deletion at p16 region were present in five of 48 cases (10.4%); and missense mutation were detected in three of 48 cases (6.3%), The overall frequency of p16 alterations, including homozygous deletion, mutation and hypermethylation, in HCC tumors was 70.8% (34 of 48 cases), These findings suggest that: (a) the inactivation of the p16 is a frequent event in HCC; (b) the p16 gene is inactivated by multiple mechanisms including homozygous deletion, promoter hypermethylation and point mutation; (c) the most common somatic alteration of the p16 gene in HCC is de novo hypermethylation of the 5' CpG island; and (d) in contrast to other studies, high frequency of genomic alterations are not uncommon in the 9p21 of the p16 gene. Our results strongly suggest that the p16 gene plays an important role in the pathogenesis of HCC.

着者Liew CT, Li HM, Lo KW, Leow CK, Chan JYH, Hin LY, Lau WY, Lai PBS, Lim BK, Huang J, Leung WT, Wu S, Lee JCK
期刊名称Oncogene
出版年份1999
月份1
日期21
卷号18
期次3
出版社STOCKTON PRESS
页次789 - 795
国际标準期刊号0950-9232
电子国际标準期刊号1476-5594
语言英式英语

关键词hepatocellular carcinoma; homozygous deletion; hypermethylation; mutation; p16
Web of Science 学科类别Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY; Genetics & Heredity; GENETICS & HEREDITY; Oncology; ONCOLOGY

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