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.
Description
IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation. - PubMed - NCBI
%0 Journal Article
%1 Oktay:2016:Sci-Rep:27282637
%A Oktay, Y
%A Ülgen, E
%A Can, Ö
%A Akyerli, C B
%A Yüksel, Ş
%A Erdemgil, Y
%A Durası, I M
%A Henegariu, O I
%A Nanni, E P
%A Selevsek, N
%A Grossmann, J
%A Erson-Omay, E Z
%A Bai, H
%A Gupta, M
%A Lee, W
%A Turcan, Ş
%A Özpınar, A
%A Huse, J T
%A Sav, M A
%A Flanagan, A
%A Günel, M
%A Sezerman, O U
%A Yakıcıer, M C
%A Pamir, M N
%A Özduman, K
%D 2016
%J Sci Rep
%K IDH IDH1 MUSTREAD cancer-research fulltext glioma
%P 27569-27569
%R 10.1038/srep27569
%T IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation
%U https://www.ncbi.nlm.nih.gov/pubmed/27282637
%V 6
%X 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.
@article{Oktay:2016:Sci-Rep:27282637,
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.},
added-at = {2018-12-19T12:53:38.000+0100},
author = {Oktay, Y and {\"U}lgen, E and Can, {\"O} and Akyerli, C B and Y{\"u}ksel, Ş and Erdemgil, Y and Durası, I M and Henegariu, O I and Nanni, E P and Selevsek, N and Grossmann, J and Erson-Omay, E Z and Bai, H and Gupta, M and Lee, W and Turcan, Ş and {\"O}zpınar, A and Huse, J T and Sav, M A and Flanagan, A and G{\"u}nel, M and Sezerman, O U and Yakıcıer, M C and Pamir, M N and {\"O}zduman, K},
biburl = {https://www.bibsonomy.org/bibtex/24f65847c76281760852c1bcddb785044/marcsaric},
description = {IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation. - PubMed - NCBI},
doi = {10.1038/srep27569},
interhash = {2276ecd3364221964f1ffaae68fd09a9},
intrahash = {4f65847c76281760852c1bcddb785044},
journal = {Sci Rep},
keywords = {IDH IDH1 MUSTREAD cancer-research fulltext glioma},
month = {06},
pages = {27569-27569},
pmid = {27282637},
timestamp = {2018-12-19T12:53:38.000+0100},
title = {IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27282637},
volume = 6,
year = 2016
}