September 4, 2018

“A cross-species analysis of the mutational landscape of cancer” (2017)

Seed Grant in Cancer and Evolution

PIs are Jeff Thorne, Jason Somarelli, Seth Faith, and Matthew Breen, North Carolina State University and Duke University. Cancer cells harbor cancer-causing mutations that are absent in normal cells. Knowing which mutations are responsible for a patient’s cancer provides insight about proper treatment. Although modern technology facilitates identification of mutations harbored by cancer cells, it is difficult to determine exactly which set of mutations actually caused the cancer. The problem is that many mutations experienced by cancer cells have little or no effect. We are hoping to develop an approach for understanding which mutations cause cancer and which do not. Evolutionary information is employed because many mutations observed in cancer have not been directly proven to induce cancer. The evolutionary information comes from comparing DNA sequences of different species. The data from non-human species are valuable because DNA differences between species represent mutations that survived; surviving mutations are unlikely to cause cancer. However, careful attention needs to given to the fact that sometimes a mutation causes cancer in one species but not in another. To properly account for this, we propose to collect new data on cancer-causing mutations from non-human species and combine these with existing human cancer data.



Somarelli JA, Boddy A, Gardner HL, et al. (2020). Improving cancer drug discovery by studying cancer across the tree of lifeMolecular Biology and Evolution 37(1): 11-17.

Rao SR, Somarelli JA, Altunel E, et al. (2020). From the clinic to the bench and back again in one dog year: How a cross-species pipeline to identify new treatments for sarcoma illuminates the path forward in precision medicineFrontiers in Oncology 10: 117.

Somarelli JA, Rupprecht G, Altunel E, et al. (2020). A comparative oncology drug discovery pipeline to identify and validate new treatments for osteosarcomaCancers 12: 3335.

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