Characterization of the Methylthioadenosine Phosphorylase Polymorphism rs7023954 - Incidence and Effects on Enzymatic Function in Malignant Melanoma
Limm K, Dettmer K, Reinders J, Oefner PJ, Boßerhoff AK (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 11
Pages Range: e0160348
Journal Issue: 8
DOI: 10.1371/journal.pone.0160348
Abstract
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.Val56Ile). 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.
Authors with CRIS profile
Katharina Limm
Lehrstuhl für Biochemie und Molekulare Medizin
Anja Katrin Boßerhoff
Lehrstuhl für Biochemie und Molekulare Medizin
Involved external institutions
Germany (DE)How to cite
APA:
Limm, K., Dettmer, K., Reinders, J., Oefner, P.J., & Boßerhoff, A.K. (2016). Characterization of the Methylthioadenosine Phosphorylase Polymorphism rs7023954 - Incidence and Effects on Enzymatic Function in Malignant Melanoma. PLoS ONE, 11(8), e0160348. https://doi.org/10.1371/journal.pone.0160348
MLA:
Limm, Katharina, et al. "Characterization of the Methylthioadenosine Phosphorylase Polymorphism rs7023954 - Incidence and Effects on Enzymatic Function in Malignant Melanoma." PLoS ONE 11.8 (2016): e0160348.
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