Science Express publication suggests that personalized medicine will need to include a focus on pathways that link uncommonly mutated genes.

A consortium of scientists studied the vast majority of protein-coding genes in colon and breast cancer. Their report suggests that most cancer-causing gene mutations are quite diverse and can vary from person to person.

With no higher-frequency mutations on the horizon, the researchers suggest that personalized medicines may now focus on the more complicated pathways that link these less-commonly mutated genes.

The team searched 18,191 genes representing more than 90% of the protein-coding genes in humans. They screened tissue samples from 11 breast and 11 colorectal cancers removed from patients after surgery.

The researchers compared the genetic sequence of these tumors with that of normal tissue samples from the same patients. Then, they evaluated all mutated genes in a second group of 24 samples from each cancer. A subset of the most promising mutations were studied in an additional 96 colorectal cancers.

They found that an average of 77 genes are mutated in an individual colon cancer and 81 in breast cancer. About 15 of these are likely to contribute to a cancer’s key characteristics and most genes may be different for each patient, they say.

The scientists also say that, while little is known about these uncommonly mutated genes, they can be grouped into clusters according to their pathways.  As an example, the team charted the path of nine genes less frequently mutated in breast or colon cancers. Each of the genes’ protein products interacted with an average of 25 other proteins, encoded by separate genes also found to be mutated in the cancers. This suggests that these genes converge in similar pathways, report the investigators.

The study was performed by investigators at GeneGo, Genentech, Perlegen Sciences, Agencourt Bioscience, Johns Hopkins Kimmel Cancer Center, University of South Carolina, Ireland Cancer Center, Case Western Reserve University, University Hospitals of Cleveland, Dana-Farber Cancer Institute, and University of Texas Southwestern Medical Center.

The paper is published online in the October 11 issue of Science Express.

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