Winter 2011

The discovery of genetic ‘hypermutations’ in prostate cancer may lead to better therapies



A team of researchers at the Hutchinson Center and the University of Washington has conducted the first comprehensive assessment of every gene in the genome of advanced, lethal prostate cancer. Until now, the genetic composition of such tumors had been poorly defined.

In the process, they discovered a number of potential key drivers—recurrent genetic mistakes—common to advanced prostate cancer that may contribute to disease progression.

The researchers also have identified several instances of genetic “hypermutation,” an excess of single-letter DNA “spelling errors” that could cause the cancer to become resistant to therapies commonly used to slow the progression of advanced prostate cancer, such as androgen-blocking drugs and surgical castration.

Dr. Peter Nelson
Dr. Peter Nelson
“The most interesting finding to come out of our DNA sequencing project was the discovery of three aggressive tumor types that had 10 times the number of mutations compared to the other advanced prostate cancers we studied,” said the Center’s Dr. Peter Nelson, one of the authors of the study.

“That was very surprising and unusual. We don’t know the cause of these hypermutated tumors, but the frequency of the mutations suggests these tumors might evolve very rapidly to develop resistance to therapies,” he said.

The discovery of these genetic mutations should provide clues to illuminate why some prostate cancers are lethal, and potentially could be used to develop screening tests for early detection or drug targets to slow or halt cancer growth, Nelson said.

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