B7
Genes associated with chemosensitivity or genotype in oligodendroglial tumours
Elisabeth Shaw1, Atik Baborie2, Michael Moxham2, Miguel Aguirreburualde2, Brian Haylock3, David Husband3, Daniel du Plessis2, Ross Sibson1, Peter Warnke4, Carol Walker1
1School of Cancer Studies, University of Liverpool, Liverpool, UK, 2The Walton Centre for Neurology and Neurosurgery, Liverpool, UK, 3Clatterbridge Centre for Oncology, Wirral, UK, 4Harvard Medical School, Boston, USA
Background
Oligodendrogliomas and oligoastrocytomas with 1p/19q loss are likely to respond to therapy and have longer survival. However, not all are chemosensitive and some with intact 1p/19q also respond. This study was undertaken to identify genes associated with 1p/19q loss and response to chemotherapy.
Method
Gene expression profiling of 32 oligodendroglial tumours (9 OII, 7 OAII, 6 OIII, 10 OAIII) given chemotherapy (31 PCV, 1 CCNU) was performed using RNA amplification and HGMP oligonucleotide arrays. Real-time PCR was performed for 23/32 cases and immunohistochemistry carried out in 20 OII, 25 OAII, 10 OIII, 25 OAIII.
Results
Ninety-four genes were identified that were at least 2-fold differentially expressed between tumours with intact 1p/19q and those with 1p/19q loss. Twenty-five genes were at least 2-fold differentially expressed between responders and non-responders, of which 3 were on 1p or 19q. Real-time PCR analysis confirmed array data in 11/13 selected genes. GFRA1, FAP, RASD1, SSBP2 and HDAC4 were associated with response. Prolonged progression free survival was associated with increased expression of INA and GFRA1 and decreased expression of SSBP2 and FAP. IQGAP1 transcript levels were down-regulated in tumours with 1p/19q loss. IQGAP1 protein expression correlated with array and PCR data. In the wider clinical series, over-expression of IQGAP1 protein was associated with high-grade (p=0.0002), intact 1p/19q (p=0.0003) and oligoastrocytic histological subtype (p=0.003).
Conclusion
Expression profiling of gliomas has identified genes differentially expressed according to molecular genetics and response, of which GFRA1 and FAP are novel in glioma. IQGAP1 may have potential diagnostic utility.
