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Downregulation of methylthioadenosin phosphorylase by homozygous deletion in gastric carcinoma.
- Source :
-
Genes, chromosomes & cancer [Genes Chromosomes Cancer] 2011 Jun; Vol. 50 (6), pp. 421-33. Date of Electronic Publication: 2011 Mar 15. - Publication Year :
- 2011
-
Abstract
- The methylthioadenosine phosphorylase (MTAP) gene is located on 9p21 telomeric to the CDKN2A tumor suppressor gene. Loss of MTAP gene is frequently associated with CDKN2A homozygous deletion. Although the homozygous deletion of MTAP has been reported in various human cancers, its function in gastric carcinogenesis is unknown. Here, we determined the status of the MTAP gene by using a combination of array-based comparative genomic hybridization and oligonucleotide microarray. It was found that MTAP was deleted and downregulated in 2 of 10 gastric cancer cell lines. Of the 494 primary gastric carcinomas examined, MTAP expression at the protein level was reduced in 59 (11.9%). Furthermore, a lack of MTAP expression was found to be associated with poor survival (P = 0.038). The genomic loss of MTAP and CDKN2A in gastric carcinomas was investigated by quantitative real-time PCR. Among 20 gastric carcinomas, two cases showed deletion of both MTAP and CDKN2A, and three samples showed homozygous deletion of MTAP, but not of CDKN2A. An analysis of gastric carcinomas revealed that reduced MTAP expression correlated significantly with a genomic deletion. Furthermore, functional assays by transfecting the siRNA or the expressional cDNA into gastric cancer cell lines demonstrated that MTAP regulates cell growth and invasion. The present study suggests that MTAP plays an important role in the regulation of gastric carcinogenesis and, in particular, that MTAP loss is implicated in some way with tumor growth via the modulation of cellular properties, which, in turn, suggests that MTAP has therapeutic applications.<br /> (Copyright © 2011 Wiley-Liss, Inc.)
- Subjects :
- Carcinoma pathology
Cell Line, Tumor
Comparative Genomic Hybridization
Female
Homozygote
Humans
Male
Neoplasm Staging
Oligonucleotide Array Sequence Analysis
Stomach Neoplasms pathology
Carcinoma genetics
Cyclin-Dependent Kinase Inhibitor p16 genetics
Gene Expression Regulation, Neoplastic
Purine-Nucleoside Phosphorylase genetics
Sequence Deletion
Stomach Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-2264
- Volume :
- 50
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Genes, chromosomes & cancer
- Publication Type :
- Academic Journal
- Accession number :
- 21412930
- Full Text :
- https://doi.org/10.1002/gcc.20867