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Genetic risk variants in the CDKN2A/B, RTEL1 and EGFR genes are associated with somatic biomarkers in glioma.

Ghasimi S, Wibom C, Dahlin AM, Brännström T, Golovleva I, Andersson U, Melin B - J. Neurooncol. (2016)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.

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.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemical staining for p53 and mutated IDH1. Expression of p53 was scored in four different categories: a negative, b faint expression, c moderate expression, d strong expression. Expression of mutated IDH1 was scored for either e negative, or f positive
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Fig1: Immunohistochemical staining for p53 and mutated IDH1. Expression of p53 was scored in four different categories: a negative, b faint expression, c moderate expression, d strong expression. Expression of mutated IDH1 was scored for either e negative, or f positive

Mentions: Based on proliferation index, 46 of 91 glioma tumors were considered less aggressive and 45 of 91 were more aggressive. Expression of mutated IDH1 was found in 15 of 90 glioma tumors, whereas 4 of 57 cases in the glioblastoma subgroup were positive for mutated IDH1. Almost all glioma patients, 85 of 89, showed p53 expression. In the glioblastoma subgroup, 38 of 56 showed faint to moderate protein expression while 17 patients demonstrated strong p53 protein expression (Fig. 1). Due to lack of patient material and failed analyses different numbers of samples are analyzed for the different biomarkers.Fig. 1


Genetic risk variants in the CDKN2A/B, RTEL1 and EGFR genes are associated with somatic biomarkers in glioma.

Ghasimi S, Wibom C, Dahlin AM, Brännström T, Golovleva I, Andersson U, Melin B - J. Neurooncol. (2016)

Immunohistochemical staining for p53 and mutated IDH1. Expression of p53 was scored in four different categories: a negative, b faint expression, c moderate expression, d strong expression. Expression of mutated IDH1 was scored for either e negative, or f positive
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835517&req=5

Fig1: Immunohistochemical staining for p53 and mutated IDH1. Expression of p53 was scored in four different categories: a negative, b faint expression, c moderate expression, d strong expression. Expression of mutated IDH1 was scored for either e negative, or f positive
Mentions: Based on proliferation index, 46 of 91 glioma tumors were considered less aggressive and 45 of 91 were more aggressive. Expression of mutated IDH1 was found in 15 of 90 glioma tumors, whereas 4 of 57 cases in the glioblastoma subgroup were positive for mutated IDH1. Almost all glioma patients, 85 of 89, showed p53 expression. In the glioblastoma subgroup, 38 of 56 showed faint to moderate protein expression while 17 patients demonstrated strong p53 protein expression (Fig. 1). Due to lack of patient material and failed analyses different numbers of samples are analyzed for the different biomarkers.Fig. 1

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.

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.

No MeSH data available.


Related in: MedlinePlus