Molecular characterization of a novel BR-2 gene that is down-regulated in human low grade glioma tumors.

Using the technique of differential hybridization of a human fetal brain library, we have identified a novel gene, brain 2 (BR-2). This gene is expressed in normal brain but has low or no expression in human oligodendrogliomas and other brain tumor samples. We have cloned and sequenced the full-length cDNA corresponding to this gene. A data base search for the nucleotide sequence homology was performed for BR-2. BR-2 sequence showed strong homolog to a human genomic clone from chromosome 2. Moderate sequence homology was observed between BR-2 and an EST from a human placenta library. Multiple tissue dot blot analysis indicated that the BR-2 gene is expressed in a number of tissues including brain, heart, lung, placenta, lymph node, trachea and kidney. The BR-2 gene is also expressed in fetal heart, spleen and lung tissue. An extremely high level of BR-2 expression is observed in the left atrium of the heart. Low or no expression of BR-2 expression is observed in sixteen human cancer cell lines. RT-PCR analysis indicated that the BR-2 gene is expressed at high levels in two of the five normal brain tissue samples analyzed. Except for low expression in one oligodendroglioma, no expression of BR-1 gene was observed in eight anaplastic astrocytomas and glioblastoma multiforme tissue samples. Four of nine glioblastoma tumor cell lines did show a low level of BR-2 expression. On the basis of its expression and sequence, we conclude that BR-2 is a novel gene with unique expression properties in human brain tumors.