Researchers Provide Systems-Level Dissection of Regulatory Perturbations in Cancer

A team of Princeton University scientists has developed a systems biology approach to list the ways a particular cancerous cell has gone wrong. Using this algorithm they were able to systematically categorize and pinpoint the alterations in cancer pathways, revealing the underlying regulatory code in DNA.

Their work is published in the December 11 issue of Molecular Cell in an article titled “Revealing Global Regulatory Perturbations across Human Cancers.”

The researchers developed an algorithm to sort through the behavior of each of 20,000 genes operating in a tumor cell and to detect as well as track changes in protein expression. The algorithm scans the DNA sequence of a given cell and deciphers which sequences are controlling what pathways and whether any are acting differently from the norm. By deciphering the patterns, the scientists can conjure up the genetic regulatory code that is underlying a particular cancer.

“At the present moment, we lump a lot of cancers together and use the same therapy,” points out Saeed Tavazoie, a professor in the department of molecular biology at the Lewis-Sigler Institute for Integrative Genomics, who led the research. “In the future, we are aiming to be much more precise about treating the exact processes that were perturbed by the mutations.”

Pathologists presently examining the tumors of sick patients analyze a small set of tumor characteristics to determine the diagnostic and prognostic class to which the cells belong. The Princeton group believes that its systems biology approach could give practitioners an encyclopedic accounting of the alterations in problem cells, spelling out the nature of the disease in much greater detail.