Affiliations: School of Cancer Studies, University of Liverpool, Liverpool, UK | Clatterbridge Centre for Oncology, Clatterbridge Hospital, Bebington, Wirral, UK | Salford Royal Hospital and Clinical Neurosciences Research Group, University of Manchester, Manchester, UK | Department of Neurosurgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Note: [] Corresponding author: Dr. Elisabeth Shaw, Cancer Research Centre, School of Cancer Studies, University of Liverpool, 200 London Road, Liverpool, L3 9TA, UK. Tel.: +44 151 794 8862; Fax: +44 151 794 8925; E-mail: [email protected].
Abstract: Background: Oligodendroglial tumors with 1p/19q loss are more likely to be chemosensitive and have longer survival than those with intact 1p/19q, but not all respond to chemotherapy, warranting investigation of the biological basis of chemosensitivity. Methods: Gene expression profiling was performed using amplified antisense RNA from 28 oligodendroglial tumors treated with chemotherapy (26 serial stereotactic biopsy, 2 resection). Expression of differentially expressed genes was validated by real-time PCR. Results: Unsupervised hierarchical clustering showed clustering of multiple samples from the same case in 14/17 cases and identified subgroups associated with tumor grade and 1p/19q status. 176 genes were differentially expressed, 164 being associated with 1p/19q loss (86% not on 1p or 19q). 94 genes differed between responders and non-responders to chemotherapy; 12 were not associated with 1p/19q loss. Significant differential expression was confirmed in 11/13 selected genes. Novel genes associated with response to therapy included SSBP2, GFRA1, FAP and RASD1. IQGAP1, INA, TGIF1, NR2F2 and MYCBP were differentially expressed in oligodendroglial tumors with 1p/19q loss. Conclusion: Gene expression profiling using serial stereotactic biopsies indicated greater homogeneity within tumors than between tumors. Genes associated with 1p/19q status or response were identified warranting further elucidation of their role in oligodendroglial tumors.
