Patterns in cancer’s chaos illuminate tumor evolution

Stephanie Dutchen in Harvard News:

For decades since the “oncogene revolution,” cancer research has focused on mutations—changes in the DNA code that abnormally activate genes that promote cancer, called oncogenes, or deactivate genes that suppress cancer. The role of aneuploidy—in which entire chromosomes or chromosome arms are added or deleted—has remained largely unstudied. Elledge and his team, including research fellow and first author Teresa Davoli, suspected that aneuploidy has a significant role to play in cancer because missing or extra chromosomes likely affect genes involved in tumor-related processes such as cell division and DNA repair.

To test their hypothesis, the researchers developed a computer program called TUSON (Tumor Suppressor and Oncogene) Explorer together with Wei Xu and Peter Park at HMS and Brigham and Women's. The program analyzed genome sequence data from more than 8,200 pairs of cancerous and normal tissue samples in three preexisting databases. They generated a list of suspected oncogenes and tumor suppressor genes based on their mutation patterns—and found many more potential cancer drivers than anticipated. Then they ranked the suspects by how powerful an effect their deletion or duplication was likely to have on cancer development. Next, the team looked at where the suspects normally appear in chromosomes. They discovered that the number of tumor suppressor genes or oncogenes in a chromosome correlated with how often the whole chromosome or part of the chromosome was deleted or duplicated in cancers. Where there were concentrations of tumor suppressor genes alongside fewer oncogenes and fewer genes essential to survival, there was more chromosome deletion. Conversely, concentrations of oncogenes and fewer tumor suppressors coincided with more chromosome duplication. When the team factored in gene potency, the correlations got even stronger. A cluster of highly potent tumor suppressors was more likely to mean chromosome deletion than a cluster of weak suppressors.

More here. (Note: Thanks to Ga)