Isolation of a novel gene, TSP50, by a hypomethylated DNA fragment in human breast cancer

A novel gene, testes-specific protease 50 (TSP50), was isolated from a huma n testes cDNA library by using a genomic DNA probe, BR50, BR50 was isolated by a modified representational difference analysis (RDA) technique due to its hypomethylated feature in a breast cancer biopsy. This altered DNA meth ylation status was also detected by BR50 in other breast and some ovarian c ancer tissues. The TSP50 gene product is a homologue to several human prote ases, which indicates that it may encode a protease-like protein. Northern analysis of 16 different types of normal human tissues suggests that TSP50 was highly and specifically expressed in human testes, which indicates that it might possess a unique biological function(s) in that organ, Methylatio n status analysis in normal human testes and other tissues showed a correla tion between DNA methylation and gene expression, Most importantly, reverse transcription-PCR analysis of 18 paired breast cancer tissues found that i n 28% of the cancer samples, the TSP50 gene was differentially expressed. T he possibility that TSP50 may be an oncogene is presently under investigati on.