IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation Journal Article
| Authors: | Oktay, Y.; Ülgen, E.; Can, Ö; Akyerli, C. B.; Yüksel, Ş; Erdemgil, Y.; Durasl, I. M.; Henegariu, O. I.; Nanni, E. P.; Selevsek, N.; Grossmann, J.; Erson-Omay, E. Z.; Bai, H.; Gupta, M.; Lee, W.; Turcan, Ş; Özplnar, A.; Huse, J. T.; Sav, M. A.; Flanagan, A.; Günel, M.; Sezerman, O. U.; Yaklcler, M. C.; Pamir, M. N.; Özduman, K. |
| Article Title: | IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation |
| Abstract: | The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17-16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94-27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association. |
| Journal Title: | Scientific Reports |
| Volume: | 6 |
| ISSN: | 2045-2322 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2016-06-10 |
| Start Page: | 27569 |
| Language: | English |
| DOI: | 10.1038/srep27569 |
| PROVIDER: | scopus |
| PMCID: | PMC4901315 |
| PUBMED: | 27282637 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2016 -- Source: Scopus |
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