Genes for prostate cancer mapped for the first time

By Dr. Ananya Mandal, MDFeb 13 2011

A genetic blue print that uncovers many of the mutations and genetic damage that drives prostate cancer and could lead to new treatments and better diagnosis has been found. This would mean earlier detection and new breeds of drugs to reverse the damage. Also each patient could have his own “cancer chart” made so that his treatment is personalized. The study, conducted by researchers from the Broad Institute, Dana-Farber Cancer Institute and Weill Cornell Medical College, appears in the Feb. 10 issue of Nature.

According to Dr Mike Berger, lead author at the Broad Institute at MIT and Harvard, “This is a transforming moment in understanding the underlying biology of prostate cancer… It offers the potential of new targets for treatment and earlier diagnosis of the more aggressive strains of the disease.”

All cancers have their roots in damage or mutations of DNA of formerly healthy cells acquired during a person’s lifetime. This makes them grow into abnormal tumors and spread around the body disrupting its normal processes and eventually cancer. Prostate cancer is the most prevalent cancer among British men, affecting a third of men over the age of 50 and accounting for about 10,000 deaths every year in England and Wales. It comes second after lung cancer as a killer.

Dr Berger’s team sequenced the genomes of seven different prostate cancer tumors and compared them to healthy tissues to find where they had been damaged or mutated. They found over 21,000 mutations in the seven tumours as well as more than a 100 “rearrangements” where whole sections of DNA have broken free and reattached to other parts of the genome. Small number of these changes could lead to cancer.

Researchers hope to sequence the genes of more patients over years to get a smaller number of target genes which could be hit with treatments such as chemotherapy and radiotherapy. Dr Levi Garraway said, “Whole genome sequencing gives us fascinating new insights into a category of alterations that may be especially important in prostate cancer…This first whole genome view shows us tantalizing evidence for several new prostate cancer genes that likely would have remained undiscovered had we not been taking a genome-wide approach.”

Dr Kate Holmes, the Prostate Cancer Charity’s Research Manager also said, “This is one of the first studies to examine the sequence and structure of the genetic code as a whole, rather than one or more single genes alone…This has allowed the researchers to identify specific patterns where large disruptions in the structure of the genetic code have taken place…These disruptions can rearrange the way genes fit together and the way they function, which is often associated with the development of aggressive prostate cancer.” She added, “This is interesting research that highlights a new approach to understanding the way prostate cancer develops. However, only 14 tissue biopsy samples were analyzed in total. The next stage will be to repeat the study on a much larger scale, which will be an extensive piece of work.”

Dr. Anna Ferrari, director of the Genitourinary Cancer Program at the NYU Cancer Institute said tat at present it is difficult for physicians to know if prostate cancer is going to be slow-growing, in which case doctors may monitor but not treat it, or if it will be aggressive, in which case surgery and chemotherapy may be needed. The researchers “have done a complete sequencing of the genome in prostate cancers that are very aggressive, and they found in addition to the already established alterations, new genes and new pathways that may influence the progression of the disease,” Ferrari said. “This may point to new targets for drug development and treatment strategies.”