absence of common somatic alterations in genes on 1p and 19q in oligodendrogliomas缺乏共同的体细胞基因改变1 p和19间胶质瘤.pdfVIP

Absence of Common Somatic Alterations in Genes on 1p and 19q in Oligodendrogliomas 1 2 3 1 4 Linda B. Bralten , Stephan Nouwens , Christel Kockx , Lale Erdem , Casper C. Hoogenraad , Johan M. 5 2 1 2 3 Kros , Michael J. Moorhouse , Peter A. Sillevis Smitt , Peter van der Spek , Wilfred van Ijcken , Andrew 2 1 Stubbs , Pim J. French * 1 Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands, 2 Department of Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands, 3 Center for Biomics, Erasmus Medical Center, Rotterdam, The Netherlands, 4 Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands, 5 Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands 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