Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma Journal Article

Authors: GarcĂ­a-Castellano, J. M.; Villanueva, A.; Healey, J. H.; Sowers, R.; Cordon-Cardo, C.; Huvos, A.; Bertino, J. R.; Meyers, P.; Gorlick, R.
Article Title: Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma
Abstract: Purpose: Methylthioadenosine phosphorylase (MTAP) is an enzyme essential in the salvage of cellular adenine and methionine synthesis. The MTAP gene is located in the 9p21 chromosomal region and its loss is frequently associated with deletion of the tumor suppressor genes p15INK4b and p16INK4a. The aim of this study was to investigate the frequency of molecular alterations in MTAP in osteosarcoma. Experimental Design: Samples from patients with high-grade osteosarcoma (n = 96) and three osteosarcoma cell lines (HOS, SaOS-2, and U2OS) were analyzed. Genomic DNA was analyzed for MTAP gene deletions by PCR, RNA expression was measured by semiquantitative reverse transcription-PCR, and the protein levels were measured by immunohistochemistry. Result: Deletion of at least one MTAP exon was found in 36 of 96 (37.5 %) osteosarcoma patient samples and in one of the three cell lines (HOS). In all cases in which an MTAP gene deletion was observed, there was absence of detectable mRNA and protein. Furthermore, in four osteosarcoma patients, an MTAP deletion which was not evident at diagnosis was detected in subsequent tumor samples. Conclusions: The MTAP gene is commonly deleted in osteosarcoma patient samples, leading to an absence of mRNA and protein expression; these results indicate that inhibitors of de novo purine synthesis or methionine depletion may be effective as treatments for osteosarcoma patients whose tumors fail to express MTAP.
Keywords: immunohistochemistry; osteosarcoma; adolescent; adult; child; human tissue; protein expression; bone neoplasms; unclassified drug; human cell; major clinical study; gene deletion; exons; polymerase chain reaction; cell cycle proteins; reverse transcription polymerase chain reaction; neoplasm recurrence, local; chromosome 9p; chromosomes, human, pair 9; tumor cells, cultured; transcription factors; immunoenzyme techniques; tumor suppressor gene; messenger rna; rna, messenger; tumor suppressor proteins; cyclin-dependent kinase inhibitor p16; dna primers; rna, neoplasm; dna determination; genomic dna; genes, tumor suppressor; cyclin-dependent kinase inhibitor p15; purine-nucleoside phosphorylase; polymorphism, single-stranded conformational; 5' methylthioadenosine phosphorylase; humans; human; male; female; priority journal; article; phosphorylase; purine synthesis
Journal Title: Clinical Cancer Research
Volume: 8
Issue: 3
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2002-03-01
Start Page: 782
End Page: 787
Language: English
PUBMED: 11895909
PROVIDER: scopus
Notes: Export Date: 14 November 2014 -- Source: Scopus