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Contact: Karin Eskenazi
Columbia University Medical Center


Caption: In an N-of-1 study, researchers at Columbia University use techniques from systems biology to analyze genomic information from an individual patient's tumor. The goal is to identify key genes, called master regulators (green circles), which, while not mutated, are nonetheless necessary for the survival of cancer cells. Master regulators are aberrantly activated by a few patient-specific mutations (X symbols) in driver genes (yellow circles), which are frequently mutated across large patient populations. Mutations in genes that are not upstream of master regulators, called passenger mutations (blue circles), have no effect on the tumor. Arrows in this diagram show the regulatory relationship between genes, i.e., how one gene regulates other downstream genes. Different patients with the same tumor generally present with highly distinctive mutations of the driver genes. Yet if their tumors behave similarly, their distinct mutational patterns must converge on the same master regulators. Blue arrows show how aberrant signals from genetic alterations converge on a handful of master regulator genes, which in turn activate complex genetic programs downstream that are necessary to implement one of more of the established cancer hallmarks--such as aberrant proliferation, immunoevasion, and circumvention of programmed cell death. Shutting down some of the master regulators, using one or more FDA-approved drugs, for instance, can block the communication pathway between cancer mutations and the genetic programs necessary for cancer survival, resulting in tumor regression.

Credit: Andrea Califano, Ph.D./Columbia University Medical Center

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