Gene expression in oligodendroglial tumors.
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.


CONCLUSIONS
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.
Shaw
Elisabeth J
EJ
School of Cancer Studies, University of Liverpool, Liverpool, UK. e.j.shaw@liverpool.ac.uk
Haylock
Brian
B
Husband
David
D
du Plessis
Daniel
D
Sibson
D Ross
DR
Warnke
Peter C
PC
Walker
Carol
C
D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D016000:Cluster Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult