PGP9.5 methylation in diffuse-type gastric cancer.
Diffuse-type gastric cancer (DGC) is the most deadly form of gastric cancer and is frequently accompanied by peritoneal dissemination and metastasis. The specific molecular events involved in DGC pathogenesis remain elusive. Accumulating evidence of epigenetic inactivation in tumor suppressor genes led us to conduct a comprehensive screen to identify novel methylated genes in human cancers using pharmacologic unmasking and subsequent microarray analysis. We compared differential RNA expression profiles of DGC and intestinal-type gastric cancer (IGC) cell lines treated with 5-aza-2'-deoxycytidine using microarrays containing 22,284 genes. We identified 16 methylated genes, including many novel genes, in DGC cell lines and studied PGP9.5 with particular interest. In primary gastric cancers, PGP9.5 was found to be more frequently methylated in DGCs (78%) than in IGCs (36%; DGC versus IGC, P < 0.05). Furthermore, real-time methylation-specific PCR analysis of PGP9.5 showed relatively higher methylation levels in DGC than in IGC. Our data thus implicate a molecular event common in the DGC phenotype compared with IGC.
Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University, 720 Rutland Avenue, Baltimore, MD 21205, USA.
Keishi
K
Yamashita
Hannah Lui
HL
Park
Myoung Sook
MS
Kim
Motonobu
M
Osada
Yutaka
Y
Tokumaru
Hiroshi
H
Inoue
Masaki
M
Mori
David
D
Sidransky
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D019175:DNA Methylation; D000077209:Decitabine; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
D000964:Antimetabolites, Antineoplastic; C482860:UCHL1 protein, human; D000077209:Decitabine; D043222:Ubiquitin Thiolesterase; D001374:Azacitidine