Methylation of p16 CpG islands associated with malignant transformation of gastric dysplasia in a population-based study.
OBJECTIVE
Inactivation of p16 by aberrant methylation of CpG islands is a frequent event in carcinomas and precancerous lesions of various organs, including the stomach. The aim of this study is to investigate the relationship between p16 methylation and malignant transformation of human gastric dysplasia (DYS) based on follow-up endoscopic screening in a high-risk population.


METHODS
Genomic DNA samples were extracted from paraffin blocks of gastric mucosal biopsies that were histopathologically diagnosed as low-grade DYS from patients who developed gastric carcinomas [GCs (n = 21)] and those that did not do so (n = 21) during 5 years of follow-up. The methylation status of p16 CpG islands of each sample was detected by methylation-specific PCR, denatured high-performance liquid chromatography, and sequencing.


RESULTS
Aberrant p16 methylation was observed in 5 of 21 samples of DYS that progressed to GC but in 0 of 21 samples that did not progress to GC (P = 0.048, two-sided). Sequencing results confirmed that all CpG sites were methylated in the analyzed sequence from these five p16-methylated cases. Furthermore, p16 methylation was also observed in the five subsequent GCs. Unmethylated p16 CpG islands were detected in all of the samples without p16 methylation.


CONCLUSIONS
Our findings suggest p16 methylation is correlated with the malignant transformation of gastric DYS, and p16 methylation might be a useful biomarker for prediction of malignant potential of gastric DYS.
Sun
Yu
Y
Peking University School of Oncology and Beijing Institute for Cancer Research, Beijing, People's Republic of China.
Deng
Dajun
D
You
Wei-Cheng
WC
Bai
Hua
H
Zhang
Lian
L
Zhou
Jing
J
Shen
Lin
L
Ma
Jun-Ling
JL
Xie
Yu-Quan
YQ
Li
Ji-You
JY
D000328:Adult; D001483:Base Sequence; D001706:Biopsy; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012306:Risk; D017422:Sequence Analysis, DNA; D013272:Stomach Diseases / Q000235:genetics*; D013447:Sulfites / Q000737:chemistry; D013997:Time Factors
D019941:Cyclin-Dependent Kinase Inhibitor p16; D013447:Sulfites; D004247:DNA