Cancer Evolution Is Associated with Pervasive Positive Selection on Globally Expressed Genes

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Cancer is a short-term evolutionary process that occurs within our bodies. Here, we demonstrate that the cancer evolutionary process differs greatly from other evolutionary processes. Most evolutionary processes are dominated by purifying selection (that removes harmful mutations). In contrast, in cancer evolution the dominance of purifying selection is much reduced, allowing for an easier detection of the signals of positive selection (that increases the likelihood beneficial mutations will persist). Mutations affected by positive selection within tumors are particularly interesting, as these are the mutations that allow cancer cells to acquire new capabilities important for transformation, tumor maintenance, drug resistance and metastasis. We demonstrate that, within tumors, positive selection strongly affects somatic mutations occurring within genes that are expressed globally, across all human tissues. Fitting with this, we show that genes that are already known to be involved in cancer tend to more often be globally expressed across tissues. However, even when such known cancer genes are removed from consideration, there is significantly more positive selection on the remaining globally expressed genes, suggesting that they are enriched for yet undiscovered cancer related functions. The results we present are important both for understanding cancer as an evolutionary process and to the continuing quest to identify new genes and pathways contributing to cancer.

Vyšlo v časopise: Cancer Evolution Is Associated with Pervasive Positive Selection on Globally Expressed Genes. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004239
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004239

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