Genes Indicate Early Prostate Cancer

In a new study, scientists analyzing sets of microarray data have identified several genes whose rearrangements in prostate cancer cells appear to play a role in the development and progression of the disease and therefore may aid detection of early disease. The findings were reported in the October 28, 2005, issue of Science.

The investigators used an innovative process called cancer outlier profile analysis (COPA) for selection of leading cancer-related over-expressed genes. COPA data allowed them to identify two new fusion genes: TMPRSS2-ERG and TMPRSS2-ETV1. These genes were formed by fusion of the TMPRSS2 gene--which is specifically related to the prostate--to the ERG or the ETV1 gene. COPA analysis of 221 historical cases (167 tumors and 54 benign prostate tissue samples) showed that either ERG or ETV1 were over-expressed in 95 of the 167 (57%) tumor samples, while there was no over-expression of either ERG or ETV1 in benign prostate tissue.

In a study of 22 prostate cancer tissues, 20 (91%) showed over-expression of ERG or ETV1 and also showed fusion with the TMPRSS2 gene, suggesting that the juxtaposition of ERG or ETV1 to the TMPRSS2 gene resulted in over-expression of these gene sequences. The researchers noted that this is the first evidence that recurrent rearrangements of genes can occur in cancers derived from epithelial cells

"This finding may have important implications for the understanding of the prostate cancer disease process and the development of potential therapies to arrest this process,” said lead author, Arul Chinnaiyan, M.D., Ph.D., of the University of Michigan Medical School (Ann Arbor, USA).

"The finding of a fused gene in prostate cancer is creating a new frontier in developing tests for earlier detection of cancer and molecular targeting,” said Sudhir Srivastava, Ph.D., director of the Early Detection Research Network of the National Cancer Institute (NCI, Bethesda, MD, USA), which sponsored the research.




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