Adverse prognosis of epigenetic inactivation in RUNX3 gene at 1p36 in human pancreatic cancer.
Alteration in transforming growth factor-beta signalling pathway is one of the main causes of pancreatic cancer. The human runt-related transcription factor 3 gene (RUNX3) is an important component of this pathway. RUNX3 locus 1p36 is commonly deleted in a variety of human cancers, including pancreatic cancer. Therefore, we examined genetic and epigenetic alterations of RUNX3 in human pancreatic cancer. Thirty-two patients with pancreatic cancer were investigated in this study. We examined the methylation status of RUNX3 promoter region, loss of heterozygosity (LOH) at 1p36, and conducted a mutation analysis. The results were compared with clinicopathological data. Promoter hypermethylation was detected in 20 (62.5%) of 32 pancreatic cancer tissues, confirmed by sequence of bisulphite-treated DNA. Loss of heterozygosity was detected in 11 (34.3%) of 32 pancreatic cancers. In comparison with clinicopathological data, hypermethylation showed a relation with a worse prognosis (P=0.0143). Hypermethylation and LOH appear to be common mechanisms for inactivation of RUNX3 in pancreatic cancer. Therefore, RUNX3 may be an important tumour suppressor gene related to pancreatic cancer.
Nomoto
S
S
Department of Surgery II, Graduate School & Faculty of Medicine, University of Nagoya, Nagoya, Japan. snomoto@med.nagoya-u.ac.jp
Kinoshita
T
T
Mori
T
T
Kato
K
K
Sugimoto
H
H
Kanazumi
N
N
Takeda
S
S
Nakao
A
A
D000328:Adult; D000368:Aged; D002878:Chromosomes, Human, Pair 1; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D005260:Female; D020868:Gene Silencing; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016019:Survival Analysis; D016212:Transforming Growth Factor beta / Q000378:metabolism
D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human; D016212:Transforming Growth Factor beta