COLON AND RECTAL CANCERS ARE GENETICALLY THE SAME

July 20, 2012 — In multiple types of genomic analyses, colon and rectal cancer results were nearly indistinguishable, according to a comprehensive molecular characterization of these cancers by the Cancer Genome Atlas (TCGA) Network.

Their work, which is based on a study of 224 tumors, was published online July 18 in Nature.

The Cancer Genome Atlas generates genomic data for cancers that point to potential targets for treatment, according to information provided by the National Cancer Institute (NCI).

The pattern of genomic alterations in colon and rectal tissues was the same, regardless of anatomic location or origin within the colon or the rectum. Because of this, the 2 cancer types can be grouped as 1, conclude the researchers, led by Raju Kucherlapati, MD, PhD, who is the Paul C. Cabot Professor of Genetics and Professor of Medicine at Harvard Medical School, Boston, Massachusetts, Initially, the TCGA Research Network studied colon tumors as though they were distinct from rectal tumors.

The Cancer Genome Atlas project is funded by the NCI and the National Human Genome Research Institute to the tune of $100 million a year.

"This finding of the true genetic nature of colon and rectal cancers is an important achievement in our quest to understand the foundations of this disease," Francis S. Collins, MD, PhD, director of the National Institutes of Health, said in a news release. "The data and knowledge gained here have the potential to change the way we diagnose and treat certain cancers."

"We really have a much better and more comprehensive view of all the types of changes that are critical for colon cancer and rectal cancer to develop," Dr. Kucherlapati told Medscape Medical News. "This is probably the largest and most comprehensive study of its nature in this cancer. Nobody in the past has analyzed this many tumor samples with all of these different applied forms at the same time."

The study also found several recurrent genetic errors that contribute to colorectal cancer. For example, there is known to be a negative link between the aggressiveness of colorectal tumors and hypermutation, a phenomenon in which the rate of genetic mutation is abnormally high because the normal DNA repair mechanisms are disrupted.

In the current study, 16% of the samples were found to be hypermutated. Of these, three quarters exhibited microsatellite (a repetitive section of DNA in the genome) instability, which can sometimes be a sign of a better prognosis.

If mutations occur in the genes responsible for maintain those regions of the genome, the microsatellites may become longer or shorter, according to the NCI.

The study showed that 24 genes were mutated in a significant number of cases. In addition to genes found through prior research (eg, APC, ARIDIA, FAM123B/WTX, TP53, SMAD4, PIK3CA, and KRAS), the researchers identified other genes (ARIDIA, SOX9, and FAM123B/WTX) as potential drivers of this cancer when mutated.

In the release, Harold E. Varmus, MD, director of the NCI, said: "While it may take years to translate this foundational genetic data on colorectal cancers into new therapeutic strategies and surveillance methods, this genetic information unquestionably will be the springboard for determining what will be useful clinically against colorectal cancers."

The researchers also identified the ERBB2 and IGF2 as being mutated or overexpressed in colorectal cancer, and therefore, as potential drug targets. These genes are involved in regulating cell proliferation and were seen to be frequently overexpressed in colorectal tumors.

This finding "points to a potential drug therapy strategy in which inhibition of the products of these genes would slow progression of the cancer," the NCI stated.

A new era of drug testing may be spawned by the research, suggested Dr. Kucherlapati.

"Suddenly, for a tumor type for which there was a limited therapeutic approach, these studies now open up a whole spectrum of approaches that can be tested," he said. "There is a great opportunity to clinically test all of these new targets by testing the tumors from each patient, finding out what kinds of changes they have, and trying to direct them into an appropriate clinical trial. And if the therapies are successful, then of course they will become the standard therapy in the future."

Dr. Kucherlapati has disclosed no relevant financial relationships.

Nature. 2012;487:330-337. Full text