Researchers in Michigan say they have identified a genetic anomaly that may drive the aggressive spread of some prostate tumors.

Writing in Cancer Discovery (2011;1;33-41), they report that mutations of a gene called KRAS appears to play a key role in some metastatic prostate cancers. 

KRAS is known to play a role in numerous cancers, but in the past has rarely been associated with prostate cancer (PCa). Now, investigators have demonstrated that a mutation in the KRAS gene, in which two pieces of the chromosome change places and fuse together, is seen only in metastatic PCa.

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“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, Director of the Michigan Center for Translational Pathology at the University of Michigan Cancer Center in Ann Arbor. “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 colleagues identified a prostate-specific gene called TMPRSS2 that fuses with a cancer-causing gene called ERG. In 2010, the team discovered gene fusions that occur in a pathway called RAF. In this new study, the researchers found that the KRAS gene fusion occurred only in cells that did not have the more common gene fusion. “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 explained.

Additionally, the new findings imply that PCa, like breast cancer, likely has different subtypes that will need different targeted treatment strategies. Dr. Chinnaiyan said he estimates that the KRAS rearrangement occurs in 1% of PCa tumors, but may be present in a higher percentage of metastatic disease.