Public release date: 25-Apr-2013 [ | E-mail | Share ]

Contact: Lauren Woods law2014@med.cornell.edu 646-317-7401 Weill Cornell Medical College

Cancer is typically thought to develop after genes gradually mutate over time, finally overwhelming the ability of a cell to control growth. But a new closer look at genomes in prostate cancer by an international team of researchers reveals that, in fact, genetic mutations occur in abrupt, periodic bursts, causing complex, large scale reshuffling of DNA driving the development of prostate cancer.

In the April 25 issue of Cell, the scientists, led by researchers from Weill Cornell Medical College, the Broad Institute, Dana-Farber Cancer Institute and the University of Trento in Italy, dub this process "punctuated cancer evolution," akin to the theory of human evolution that states changes in a species occur in abrupt intervals. After discovering how DNA abnormalities arise in a highly interdependent manner, the researchers named these periodic disruptions in cancer cells that lead to complex genome restructuring "chromoplexy."

"We believe chromoplexy occurs in the majority of prostate cancers, and these DNA shuffling events appear to simultaneously inactivate genes that could help protect against cancer," says the study's co-lead investigator Dr. Mark Rubin, who is director of the recently-established Institute for Precision Medicine at Weill Cornell Medical College and NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

"Knowing what actually happens over time to the genome in cancer may lead to more accurate diagnosis of disease and, hopefully, more effective treatment in the future," says Dr. Rubin, also the Homer T. Hirst III Professor of Oncology, professor of pathology and laboratory medicine and professor of pathology in urology at Weill Cornell and a pathologist at NewYork-Presbyterian/Weill Cornell. "Our findings represent a new way to think about cancer genomics as well as treatment in prostate and, potentially, other cancers."

The discovery of "chromoplexy" came after the research team worked collaboratively to sequence the entire genomes of 57 prostate tumors and compare those findings to sequences in matched normal tissue.

Co-lead investigator Dr. Levi Garraway, of the Broad Institute and Dana-Farber Cancer Institute, and his collaborators then tracked how genetic alterations accumulated during cancer development and progression. They used advanced computer techniques to identify periodic bursts of genetic derangements.

"We have, for the first time, mapped the genetic landscape of prostate cancer as it changes over time," says Dr. Garraway, a senior associate member of the Broad Institute and associate professor at the DanaFarber Cancer Institute and Harvard Medical School. "The complex genomic restructuring we discovered, which occurs at discrete times during tumor development, is a unique and important model of carcinogenesis which likely has relevance for other tumor types."

Co-senior author Dr. Francesca Demichelis, assistant professor at the Centre for Integrative Biology at the University of Trento who also serves as adjunct assistant professor of computational biomedicine at Weill Cornell, worked with her collaborators to understand how widespread the DNA mutations and alterations seen in the tumors were across the cancer samples, and what that might mean in terms of cancer progression and, potentially, treatment. "Information about what alterations are common, and which aren't, will most likely help guide us in terms of cancer drug use and patient response," says Dr. Demichelis.

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Periodic bursts of genetic mutations drive prostate cancer

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