Preliminary evidence of different selection pressures on cancer cells as compared to normal tissues
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RESEARCH
Open Access
Preliminary evidence of different selection pressures on cancer cells as compared to normal tissues Katie Ovens1 and Christopher Naugler2* * Correspondence: Christopher. [email protected] 2 Calgary Laboratory Services and Department of Pathology and Laboratory Medicine, University of Calgary, C414, Diagnostic and Scientific Centre, 9, 3535 Research Road NW, Calgary, AB T2L 2K8, Canada Full list of author information is available at the end of the article
Abstract Background: Cancer is characterized by both a high mutation rate as well as high rates of cell division and cell death. We postulate that these conditions will result in the eventual mutational inactivation of genes not essential to the survival of the cancer cell, while mutations in essential genes will be eliminated by natural selection leaving molecular signatures of selection in genes required for survival and reproduction. By looking for signatures of natural selection in the genomes of cancer cells, it should therefore be possible to determine which genes have been essential for the development of a particular cancer. Methods: We provide a proof of principle test of this idea by applying a test of neutrality (Nei-Gojobori Z-test of selection) to 139 cancer-related nucleotide sequences obtained from GenBank representing 46 cancer-derived genes. Results: Among cancer associated sequences, 10 genes showed molecular evidence of selection. Of these 10 genes, four showed molecular evidence of selection in non-cancer transcripts. Among non-cancer associated sequences, eight genes showed molecular evidence of selection, with four of these also showing selection in the cancer associated sequences. Conclusions: These results provide preliminary evidence that the same genes may experience different selection pressures within normal and cancer tissues. Application of this technique could identify genes under unique selection pressure in cancer tissues and thereby indicate possible targets for therapeutic intervention.
Introduction Cancer cell clones evolve over the lifespan a tumour [1-3]. The selective pressures driving this clonal evolution are myriad and may include microenvironmental factors, immune system surveillance, competition with other cancer and somatic cells, and selective killing of cancer cells by surgery, chemotherapy and radiation [2-9]. Two features of cancer portend intense natural selection among cancer cells. The first is the observation that cancer cells (at least in the later stages of growth) experience a high rate of cell death [10]. The second is the greatly increased rate of mutations in cancer cells [11-16]. For example, a recent large scale study identified mutations in 11% of protein coding genes examined over 756 cancer cell lines [17]. Many of these mutations, even if they change the resulting protein sequence of the gene product may be © 2012 Ovens and Naugler; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creati
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