title: Absence of common somatic alterations in genes on 1p and 19q in oligodendrogliomas.
abstract: A common and histologically well defined subtype of glioma are the oligodendroglial brain tumors. Approximately 70% of all oligodendrogliomas have a combined loss of the entire 1p and 19q chromosomal arms. This remarkably high frequency suggests that the remaining arms harbor yet to be identified tumor suppressor genes. Identification of these causal genetic changes in oligodendrogliomas is important because they form direct targets for treatment. In this study we therefore performed targeted resequencing of all exons, microRNAs, splice sites and promoter regions residing on 1p and 19q on 7 oligodendrogliomas and 4 matched controls. Only one missense mutation was identified in a single sample in the ARHGEF16 gene. This mutation lies within- and disrupts the conserved PDZ binding domain. No similar ARHGEF16 mutations or deletions were found in a larger set of oligodendrogliomas. The absence of common somatic changes within genes located on 1p and 19q in three out of four samples indicates that no additional "second hit" is required to drive oncogenic transformation on either chromosomal arm.
authors.affiliation: Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Linda B
authors.initials: LB
authors.lastname: Bralten
authors.forename: Stephan
authors.initials: S
authors.lastname: Nouwens
authors.forename: Christel
authors.initials: C
authors.lastname: Kockx
authors.forename: Lale
authors.initials: L
authors.lastname: Erdem
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
authors.forename: Johan M
authors.initials: JM
authors.lastname: Kros
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Moorhouse
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sillevis Smitt
authors.forename: Peter
authors.initials: P
authors.lastname: van der Spek
authors.forename: Wilfred
authors.initials: W
authors.lastname: van Ijcken
authors.forename: Andrew
authors.initials: A
authors.lastname: Stubbs
authors.forename: Pim J
authors.initials: PJ
authors.lastname: French
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics*; D056726:Genetic Association Studies; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009837:Oligodendroglioma / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: C556035:ARHGEF16 protein, human; D020662:Guanine Nucleotide Exchange Factors