Chordoma Foundation


MTAP (Methylthioadenosine Phosphorylase) is a gene encodes an enzyme necessary for cells to metabolize polyamines and to salvage certain amino acids (adenine and methionine).

Location: MTAP on Chromosome 9p21

MTAP appears to be expressed in all human tissues. Losing MTAP expression makes cells entirely dependent on de novo purine synthesis. Tumor cells that lose MTAP expression may be therefore be sensitive to inhibitors of purine biosynthesis.

MTAP in Chordoma

MTAP has been implicated in a variety of human cancers, including chordoma, because it is often co-deleted with the tumor suppressor gene CDKN2A (p16) on chromosome 9. Because loss of MTAP makes tumor cells sensitive to substances that inhibit purine biosynthesis, the subset of chordoma patients whose tumors lack MTAP expression might respond to treatment with such agents.1 This page contains a summary of published research evaluating the role of MTAP in chordoma.

Molecular Evidence

Chromosomal Abnormalities

Deletion of chromosome 9 or of regions of 9p harboring all or part of MTAP is common in chordomas. The gene is often co-deleted with the tumor suppressor gene CDKN2A (which encodes p16).2 3 4 5 6 7  Chordoma cell line U-CH1 has a deletion containining the entire MTAP gene and U-CH2 has a deletion involving a region of chromosome 9 very close to MTAP.8 MUG-Chor1 also has a deletion involving the MTAP locus.9

Protein Expression

MTAP is constitutively expressed in normal tissues, but 11 of 28 chordomas show loss of MTAP expression.10

Bertino J, Waud W, Parker W, Lubin M. Targeting tumors that lack methylthioadenosine phosphorylase (MTAP) activity: current strategies. Cancer Biol Ther. 2011;11(7):627-632. [PubMed]
Hallor K, Staaf J, Jönsson G, et al. Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation. Br J Cancer. 2008;98(2):434-442. [PubMed]
Rinner B, Weinhaeusel A, Lohberger B, et al. Chordoma characterization of significant changes of the DNA methylation pattern. PLoS One. 2013;8(3):e56609. [PubMed]
Le L, Nielsen G, Rosenberg A, et al. Recurrent chromosomal copy number alterations in sporadic chordomas. PLoS One. 2011;6(5):e18846. [PubMed]
Diaz R, Guduk M, Romagnuolo R, et al. High-resolution whole-genome analysis of skull base chordomas implicates FHIT loss in chordoma pathogenesis. Neoplasia. 2012;14(9):788-798. [PubMed]
Dewaele B, Maggiani F, Floris G, et al. Frequent activation of EGFR in advanced chordomas. Clin Sarcoma Res. 2011;1(1):4. [PubMed]
Kitamura Y, Sasaki H, Kimura T, et al. Molecular and clinical risk factors for recurrence of skull base chordomas: gain on chromosome 2p, expression of brachyury, and lack of irradiation negatively correlate with patient prognosis. J Neuropathol Exp Neurol. 2013;72(9):816-823. [PubMed]
Brüderlein S, Sommer J, Meltzer P, et al. Molecular characterization of putative chordoma cell lines. Sarcoma. 2010;2010:630129. [PubMed]
Rinner B, Froehlich E, Buerger K, et al. Establishment and detailed functional and molecular genetic characterisation            of a novel sacral chordoma cell line, MUG-Chor1. Int J Oncol. 2012;40(2):443-451. [PubMed]
Sommer J, Itani D, Homlar K, et al. Methylthioadenosine phosphorylase and activated insulin-like growth factor-1 receptor/insulin receptor: potential therapeutic targets in chordoma. J Pathol. 2010;220(5):608-617. [PubMed]

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