November 11, 2014

Protein “pockets” help ID cancer genes

Vanderbilt investigators have used a computational biology approach to uncover new cancer drivers and biomarkers of anticancer drug response.


Somatic mutations, which can occur in any cell except sperm or egg, are not inheritable.

Several recent studies have demonstrated that disease-causing mutations commonly alter protein folding, protein stability and protein-protein interactions. It has been difficult, however, to determine which somatic mutations identified in tumor samples “drive” the cancer development and which are just “along for the ride.”

Using a computational approach they developed, Zhongming Zhao, Ph.D., and colleagues systematically investigated somatic mutations located in protein “pocket” regions that, among other functions, bind small molecules, enzymes and nucleic acids.

Reporting last month in Genome Medicine, they found that somatic mutations in protein pocket regions tend to be functionally important during tumorigenesis and sensitive to anticancer drug responses. They identified four putative cancer genes that are associated with overall poor survival rates in patients with melanoma, lung or colorectal cancer.

Protein pocket-based prioritization of somatic mutations thus provides a promising approach to uncover putative cancer drivers and biomarkers of anticancer drug response.

The study was supported in part by National Institutes of Health grants LM011177, LM007450, CA095103, CA098131 and CA068485.

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