Abstract
During the last years, genome wide association studies have discovered common germline genetic variants associated with specific glioma subtypes. We aimed to study the association between these germline risk variants and tumor phenotypes, including copy number aberrations and protein expression. A total of 91 glioma patients were included. Thirteen well known genetic risk variants in TERT, EGFR, CCDC26, CDKN2A, CDKN2B,PHLDB1, TP53, and RTEL1 were selected for investigation of possible correlations with the glioma somatic markers: EGFR amplification, 1p/19q codeletion and protein expression of p53, Ki-67, and mutated IDH1. The CDKN2A/B risk variant, rs4977756, and the CDKN2B risk variant, rs1412829 were inversely associated (p = 0.049 and p = 0.002, respectively) with absence of a mutated IDH1, i.e., the majority of patients homozygous for the risk allele showed no or low expression of mutated IDH1. The RTEL1 risk variant, rs6010620 was associated (p = 0.013) with not having 1p/19q codeletion, i.e., the majority of patients homozygous for the risk allele did not show 1p/19q codeletion. In addition, the EGFR risk variant rs17172430 and the CDKN2B risk variant rs1412829, both showed a trend for association (p = 0.055 and p = 0.051, respectively) with increased EGFR copy number, i.e., the majority of patients homozygote for the risk alleles showed chromosomal gain or amplification of EGFR. Our findings indicate that CDKN2A/B risk genotypes are associated with primary glioblastoma without IDH mutation, and that there is an inverse association between RTEL1 risk genotypes and 1p/19q codeletion, suggesting that these genetic variants have a molecular impact on the genesis of high graded brain tumors. Further experimental studies are needed to delineate the functional mechanism of the association between genotype and somatic genetic aberrations.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-016-2066-4) contains supplementary material, which is available to authorized users.
Highlights
Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Glioma includes several subtypes
Our findings indicate that CDKN2A/B risk genotypes are associated with primary glioblastoma without IDH mutation, and that there is an inverse association between RTEL1 risk genotypes and 1p/19q codeletion, suggesting that these genetic variants have a molecular impact on the genesis of high graded brain tumors
Eighty glioma patients were successfully analyzed for EGFR copy number variation and 1p/19q codeletion, two samples were excluded since the ratio was below 1 and there were too few patients to make a separate group for these two samples
Summary
They have been classified solely on histopathological features, though classification is currently changing towards accounting for molecular markers as well [1]. The somatic mutations and aberrations are sometimes correlated [2], such as the link between IDH1 mutation and 1p/19q codeletion in low grade glioma [3,4,5]. Some of these markers, like IDH1 mutation and MGMT methylation, have diagnostic value and are useful prognostic and predictive factors relating to patient survival and response to treatment [6,7,8,9,10]. Like IDH1 mutation and MGMT methylation, have diagnostic value and are useful prognostic and predictive factors relating to patient survival and response to treatment [6,7,8,9,10]. 1p/19q codeletion is thought to be a distinguishing feature for oligodendroglioma and TP53
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