Low expression but infrequent genomic loss of the putative tumour suppressor DBCCR1 in astrocytoma

DBCCR1 (deleted in bladder cancer chromosomal region 1) has been reported as the gene functionally affected by frequent loss of 9q32-33 in transitional cell carcinomas of the urinary bladder. For these particular tumours, its proposed role in tumour suppression is supported both by the observation of methylation-based silencing of DBCCR1 in a large fraction of bladder cancers and by re-expression studies in bladder cancer-derived cell lines. A more general involvement of DBCCR1 in tumour development might be inferred from recent chip-based expression studies in other tumours. The present study addressed expression of DBCCR1 in gliomas, specifically in astrocytomas, using semi-quantitative RT-PCR on 25 tumours of different malignancy grade and on 5 control brain tissue samples. Genomic deletion of the DBCCR1 locus at 9q32-33 was also investigated, together with the CDKN2A locus at 9p21, by loss of heterozygosity analysis in a second series of 26 astrocytic tumours. We found that DBCCR1 mRNA expression is markedly reduced in the majority of tumour samples compared to controls, and that this reduction significantly correlates with tumour grade. Genomic loss of the DBCCR1 region was found in only 5 of 24 (21%) informative samples, with no obvious correlation to tumour grade, while loss of the CDKN2A locus was observed in 13 of 21 (62%) informative samples with high-grade tumours being affected more often. If present, LOH at 9q coincided with LOH at 9p and is then likely to reflect loss of the entire chromosome rather than a specific, potentially causative event. In contrast to the situation in bladder cancer, the prevalent inactivation of DBCCR1 seen at the expression level in astrocytomas is not primarily caused by genomic loss of the gene. Our findings support a more general role for DBCCR1 in tumour suppression with mechanisms of inactivation differing between tumour types.