Global and non-random CpG-island methylation in gastric carcinoma associated with Epstein-Barr virus.
DNA hypermethylation may play a primary role in the genesis of Epstein-Barr virus (EBV)-associated gastric carcinoma (GC) (EBVaGC). Methylation-specific PCR targeting CpG-islands demonstrated markedly increased methylation of specific genes, such as p14, p15 and p16 genes, in EBVaGC in vivo. A high frequency of methylation was observed in an EBVaGC strain of severe combined immunodeficiency mice, and the expression of methylated genes in the strain was apparently lower than the expression of the unmethylated genes in EBV-negative GC strains. Although over-expression of DNA methyltransferases (DNMTs) is known to be associated with some human cancers, real-time PCR demonstrated that DNMTs expression was suppressed in EBVaGC. The DNA methylation of specific genes, independently of DNMTs expression, may be important in the development of EBVaGC.
Chong
Ja-Mun
JM
Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033. jmchong-tky@umin.ac.jp
Sakuma
Kazuya
K
Sudo
Makoto
M
Ushiku
Tetsuo
T
Uozaki
Hiroshi
H
Shibahara
Junji
J
Nagai
Hideo
H
Funata
Nobuaki
N
Taniguchi
Hirokazu
H
Aburatani
Hiroyuki
H
Fukayama
Masashi
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002472:Cell Transformation, Viral / Q000235:genetics; D018899:CpG Islands; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000821:virology; D014412:Tumor Virus Infections / Q000235:genetics*
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D004248:DNA (Cytosine-5-)-Methyltransferases