p16INK4 is inactivated by extensive CpG methylation in human hepatocellular carcinoma
Y Matsuda, T Ichida, J Matsuzawa, K Sugimura… - Gastroenterology, 1999 - Elsevier
Y Matsuda, T Ichida, J Matsuzawa, K Sugimura, H Asakura
Gastroenterology, 1999•ElsevierBackground & Aims: The molecular status of the p16INK4 tumor-suppressor gene has not
been fully elucidated in hepatocellular carcinoma. The aim of this study was to clarify the
mechanism that gives rise to inactivation of p16INK4 in hepatocellular carcinoma. Methods:
The status of p16INK4 was evaluated in 60 hepatocellular carcinomas by
immunohistochemical staining, differential polymerase chain reaction, single-strand
conformational polymorphism, methylation-specific polymerase chain reaction, and …
been fully elucidated in hepatocellular carcinoma. The aim of this study was to clarify the
mechanism that gives rise to inactivation of p16INK4 in hepatocellular carcinoma. Methods:
The status of p16INK4 was evaluated in 60 hepatocellular carcinomas by
immunohistochemical staining, differential polymerase chain reaction, single-strand
conformational polymorphism, methylation-specific polymerase chain reaction, and …
Background & Aims
The molecular status of the p16INK4 tumor-suppressor gene has not been fully elucidated in hepatocellular carcinoma. The aim of this study was to clarify the mechanism that gives rise to inactivation of p16INK4 in hepatocellular carcinoma.
Methods
The status of p16INK4 was evaluated in 60 hepatocellular carcinomas by immunohistochemical staining, differential polymerase chain reaction, single-strand conformational polymorphism, methylation-specific polymerase chain reaction, and methylation-sensitive single nucleotide primer extension.
Results
Immunohistochemical staining showed that 29 of the 60 tumors exhibited complete loss of p16INK4 expression. High levels of DNA methylation were detected in 24 of 29 cases of hepatocellular carcinoma with negative p16INK4 expression, with methylation of 60%–85% of the CpG islands. In contrast, the level of methylation was <25% in tumors with faint p16INK4 staining, and no methylation was detected in tumors with positive immunostaining. Intragenic alteration of p16INK4 was detected in 4 cases.
Conclusions
A strong correlation was found between the extent of methylation and the degree of expression of p16INK4 in tumor tissues, indicating that epigenetic change due to extensive CpG methylation is the main cause of inactivation of p16INK4 in hepatocellular carcinoma. GASTROENTEROLOGY 1999;116:394-400
Elsevier