Genetic anomaly may drive aggressive prostate cancer

Mutations of a gene called KRAS may drive metastatic prostate cancer, say researchers from the University of Michigan, Ann Arbor.

KRAS is known to play a role in numerous cancers but is rarely associated with prostate cancer.

"This study suggests that in a rare subset of prostate cancers, KRAS rearrangement acts as a mechanism that may promote tumor progression," said senior author Arul Chinnaiyan, MD, PhD. "We speculate that prostate cancers with this rearrangement are more aggressive, since we have found them only in metastatic disease."

In 2005, Dr. Chinnaiyan and his team identified a prostate-specific gene called TMPRSS2 that fuses with a cancer-causing gene called ERG. In this new study, the researchers found the KRAS gene fusion occurred only in cells that did not have the more common gene fusion. The team also discovered in 2010 gene fusions that occur in a pathway called RAF.

"This suggests that prostate cancer can find different ways to activate a molecular pathway by creating gene rearrangements in at least these three ways," Dr. Chinnaiyan said.

This implies that, like breast cancer, prostate cancer likely has different subtypes that will need different, targeted treatment strategies. Dr. Chinnaiyan estimates the KRAS rearrangement occurs in 1% of prostate cancers but may represent a higher percentage of metastatic prostate cancer.

Results of the study appear in Cancer Discovery (2011; 1:33-41).