Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma

José M. García-Castellano, Alberto Villanueva, John H. Healey, Rebecca Sowers, Carlos Cordon-Cardo, Andrew Huvos, Joseph R. Bertino, Paul Meyers, Richard Gorlick

Research output: Contribution to journalArticle

63 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)782-787
Number of pages6
JournalClinical Cancer Research
Volume8
Issue number3
StatePublished - 2002
Externally publishedYes

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Gene Deletion
Osteosarcoma
Methionine
5'-methylthioadenosine phosphorylase
Cell Line
Polymerase Chain Reaction
Messenger RNA
Proteins
Adenine
Tumor Suppressor Genes
Genes
Reverse Transcription
Exons
Neoplasms
Research Design
Immunohistochemistry
RNA
DNA
Enzymes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

García-Castellano, J. M., Villanueva, A., Healey, J. H., Sowers, R., Cordon-Cardo, C., Huvos, A., ... Gorlick, R. (2002). Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma. Clinical Cancer Research, 8(3), 782-787.

Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma. / García-Castellano, José M.; Villanueva, Alberto; Healey, John H.; Sowers, Rebecca; Cordon-Cardo, Carlos; Huvos, Andrew; Bertino, Joseph R.; Meyers, Paul; Gorlick, Richard.

In: Clinical Cancer Research, Vol. 8, No. 3, 2002, p. 782-787.

Research output: Contribution to journalArticle

García-Castellano, JM, Villanueva, A, Healey, JH, Sowers, R, Cordon-Cardo, C, Huvos, A, Bertino, JR, Meyers, P & Gorlick, R 2002, 'Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma', Clinical Cancer Research, vol. 8, no. 3, pp. 782-787.
García-Castellano JM, Villanueva A, Healey JH, Sowers R, Cordon-Cardo C, Huvos A et al. Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma. Clinical Cancer Research. 2002;8(3):782-787.
García-Castellano, José M. ; Villanueva, Alberto ; Healey, John H. ; Sowers, Rebecca ; Cordon-Cardo, Carlos ; Huvos, Andrew ; Bertino, Joseph R. ; Meyers, Paul ; Gorlick, Richard. / Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma. In: Clinical Cancer Research. 2002 ; Vol. 8, No. 3. pp. 782-787.
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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.",
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AU - García-Castellano, José M.

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AU - Healey, John H.

AU - Sowers, Rebecca

AU - Cordon-Cardo, Carlos

AU - Huvos, Andrew

AU - Bertino, Joseph R.

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