Prostate Cancer Fusion Proteins May Become Treatment Targets

Uncontrollable reproduction of prostate cancer cells may be due in part to the formation of fusion genes that encode novel growth promoting proteins, which may themselves be targets for directed chemotherapeutic agents.

Most prostate cancers overexpress the ERG gene, and many possess fusion genes that combine ERG with other genes such as TMPRSS2 or SCL45A3. Not all of these fusion genes encode for proteins, but in a study published in the August 2009 online edition of the journal Neoplasia investigators from Weill Cornell Medical College (New York, NY, USA) reported finding a previously unidentified fusion gene that likely encodes a functional protein.

The investigators used advanced molecular biology techniques including fluorescent in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR) assays to screen 101 prostate cancers. They found that 34 carried aTMPRSS2-ERG fusion gene, while three cases harbored SCL45A3-ERG. In addition, they identified two cancers with the previously undetected NDRG1-ERG fusion gene. Unlike the TMPRSS2-ERG and SCL45A3-ERG fusions, the NDRG1-ERG fusion was predicted to encode a chimeric protein.

"The prostate cancer gene fusions, and proteins they produce, are important because they serve as a cancer-specific marker,” explained senior author Dr. Mark A. Rubin, professor of pathology and laboratory medicine at Weill Cornell Medical College. "Currently, PSA [prostate-specific antigen] testing is the standard of care, yet it is not accurate enough to predict prostate cancer, because many men may have an elevated PSA level, but have benign conditions such as inflammation of the prostate.”

"In the future, these fusions, specific to certain types of prostate cancer, may help physicians prescribe tailored therapies for their patients by avoiding the trial and error that is often associated with cancer treatments,” said Dr. Rubin. "We believe this is a first step toward providing patients with specific therapies that target individual cancer variants, and hope these findings will help doctors diagnose a patient's specific disease.”

Related Links:
Weill Cornell Medical College