Molecular characterization of a novel human brain tumor-associated gene BR-3.

Using the technique of differential hybridization of a human fetal brain library, we have identified a novel gene, brain 3 (BR-3). This gene is not expressed in normal human brain tissue samples but is expressed at high levels in human low-grade glioma tissue samples. We have cloned and sequenced the full-length cDNA corresponding to this gene. Data base search analysis indicated that the BR-3 gene has strong homology to a genomic sequence present on chromosome 1 but no homology to expressed genes. Open reading frame analysis has indicated the presence of a 71 amino acids long protein sequence. A data base search for the protein sequence homology showed no similarity to known sequences. Expression analysis of BR-3 indicated that it is expressed at high level in six out of seven low-grade glioma samples analyzed. In addition low levels of BR-3 gene expression was observed in six out of seven anaplastic astrocytoma tissue samples analyzed. BR-3 expression was observed in four of eight glioblastoma samples analyzed. Expression analysis of normal human tissues indicated that it is expressed in kidney, skeletal muscle, lung, spleen and heart. No expression of the BR-3 gene was observed in brain, liver or testes tissue. To understand the role of the BR-3 gene in cancer in general, we studied its expression in other cancer cell lines. Except for lung and ovarian carcinoma, the BR-3 gene is expressed in breast carcinoma, colon adenocarcinoma, prostatic adenocarcinoma, and pancreatic adenocarcinoma tissue samples. On the basis of its sequence, unique expression pattern, we conclude that BR-3 gene product may play a critical role in the genesis of human gliomas tumors.