title: EGFR gene variants are associated with specific somatic aberrations in glioma.
abstract: A number of gene variants have been associated with an increased risk of developing glioma. We hypothesized that the reported risk variants may be associated with tumor genomic instability. To explore potential correlations between germline risk variants and somatic genetic events, we analyzed matched tumor and blood samples from 95 glioma patients by means of SNP genotyping. The generated genotype data was used to calculate genome-wide allele-specific copy number profiles of the tumor samples. We compared the copy number profiles across samples and found two EGFR gene variants (rs17172430 and rs11979158) that were associated with homozygous deletion at the CDKN2A/B locus. One of the EGFR variants (rs17172430) was also associated with loss of heterozygosity at the EGFR locus. Our findings were confirmed in a separate dataset consisting of matched blood and tumor samples from 300 glioblastoma patients, compiled from publically available TCGA data. These results imply there is a functional effect of germline EGFR variants on tumor progression.
authors.affiliation: Department of Radiation Sciences, Oncology, Computational Life Science Cluster (CLiC), Umeå University, Umeå, Sweden. carl.wibom@onkologi.umu.se
authors.forename: Carl
authors.initials: C
authors.lastname: Wibom
authors.forename: Soma
authors.initials: S
authors.lastname: Ghasimi
authors.forename: Peter
authors.initials: P
authors.lastname: Van Loo
authors.forename: Thomas
authors.initials: T
authors.lastname: Brännström
authors.forename: Johan
authors.initials: J
authors.lastname: Trygg
authors.forename: Ching
authors.initials: C
authors.lastname: Lau
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.forename: Tommy
authors.initials: T
authors.lastname: Bergenheim
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.forename: Patrik
authors.initials: P
authors.lastname: Rydén
authors.forename: Beatrice
authors.initials: B
authors.lastname: Melin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D005838:Genotype; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors