Researchers Find "On" Switches That May Play Role in Colorectal Cancer

As a direct result of the Human Genome Project, researchers report they have uncovered some of the dangerous "on” switches -- mutant genes -- that may play a role in causing cancer of the colon and rectum.

The researchers, reporting in the journal Science, said they had uncovered 14 enzyme genes that appear to get activated erroneously and then help convert normal cells into cancer cells.

These mutations likely play a role in the development of colorectal cancer, researchers said, because at least one was present in colorectal cancer cells of about 30 percent of the 182 patients taking part in the study, but none was found in healthy tissue of the patients.

Some of these mutated forms of the proteins, known as tyrosine kinases, may ultimately be good targets for drug therapy, the researchers said.

"Our findings open the door to individualized analysis and treatment of colorectal cancer," said Dr. Victor E. Velculescu, assistant professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, who led the research effort.

"With this new work, one could imagine personalized therapeutics, based on mutations in different kinase genes and designed to match the mutated TK pathways present in each patient's particular tumor DNA," he added.

To conduct this research, the investigators focused on the 138 normal TK genes that all humans contain. They sifted through more than 4 million base pairs of DNA and ultimately identified mutations in 14 of these genes.

"These mutations are truly needles in a haystack," said Velculescu.

"Without the sophisticated new technologies and knowledge developed through the Human Genome Project, it would have been impossible for us to systematically sort through the massive amount of normal DNA sequences to find the few critical mutants," added Alberto Bardelli, Ph.D., a postdoctoral fellow at Johns Hopkins.

Other Sources: Science