Limm, Katharina and Dettmer, Katja and Reinders, Joerg and Oefner, Peter J. and Bosserhoff, Anja-Katrin (2016) Characterization of the Methylthioadenosine Phosphorylase Polymorphism rs7023954-Incidence and Effects on Enzymatic Function in Malignant Melanoma. PLOS ONE, 11 (8): e0160348. ISSN 1932-6203,
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Deficiency of methylthioadenosine phosphorylase (MTAP) supports melanoma development and progression through accumulation of its substrate 5'-methylthioadenosine (MTA), which leads amongst others to a constitutive inhibition of protein arginine methyltransferases (PRMTs) and activation of the transcription factor AP-1 via the receptor ADORA2B. Genetic association studies have also suggested that genetic polymorphism in MTAP may modulate the risk of melanoma. Here, we investigated the only globally common non-synonymous single nucleotide polymorphism (SNP) reported to date for MTAP. The SNP rs7023954 is located in exon 3 (c. 166G>A), and leads to the conservative substitution of one branched-chain amino acid residue (valine) for another (isoleucine) at position 56 (p. Val56lle). Whereas genotype frequencies in normal and primary melanoma tissues or cell lines were in Hardy-Weinberg equilibrium based on cDNA amplicon sequencing, a marked (P = 0.00019) deviation was observed in metastatic melanoma tissues and cell lines due to a deficit of heterozygotes. Enzyme assays conducted on the co-dominantly expressed alleles revealed no difference in the conversion rate of MTA to adenine and 5-methylthioribose-1-phosphate, indicating that this known enzymatic activity does not modulate the tumor suppressive function of MTAP.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CUTANEOUS MELANOMA; CELL-PROLIFERATION; EXPRESSION; MTAP; PROGRESSION; SURVIVAL; RISK; 5'-DEOXY-5'-METHYLTHIOADENOSINE; MECHANISMS; VARIANTS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Apr 2019 12:07 |
| Last Modified: | 05 Apr 2019 12:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3561 |
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