--- _id: '903' abstract: - lang: eng text: 'Background: Carcinogenesis typically involves multiple somatic mutations in caretaker (DNA repair) and gatekeeper (tumor suppressors and oncogenes) genes. Analysis of mutation spectra of the tumor suppressor that is most commonly mutated in human cancers, p53, unexpectedly suggested that somatic evolution of the p53 gene during tumorigenesis is dominated by positive selection for gain of function. This conclusion is supported by accumulating experimental evidence of evolution of new functions of p53 in tumors. These findings prompted a genome-wide analysis of possible positive selection during tumor evolution. Methods: A comprehensive analysis of probable somatic mutations in the sequences of Expressed Sequence Tags (ESTs) from malignant tumors and normal tissues was performed in order to access the prevalence of positive selection in cancer evolution. For each EST, the numbers of synonymous and non-synonymous substitutions were calculated. In order to identify genes with a signature of positive selection in cancers, these numbers were compared to: i) expected numbers and ii) the numbers for the respective genes in the ESTs from normal tissues. Results: We identified 112 genes with a signature of positive selection in cancers, i.e., a significantly elevated ratio of non-synonymous to synonymous substitutions, in tumors as compared to 37 such genes in an approximately equal-sized EST collection from normal tissues. A substantial fraction of the tumor-specific positive-selection candidates have experimentally demonstrated or strongly predicted links to cancer. Conclusion: The results of EST analysis should be interpreted with extreme caution given the noise introduced by sequencing errors and undetected polymorphisms. Furthermore, an inherent limitation of EST analysis is that multiple mutations amenable to statistical analysis can be detected only in relatively highly expressed genes. Nevertheless, the present results suggest that positive selection might affect a substantial number of genes during tumorigenic somatic evolution.' acknowledgement: This work was supported by the Intramural Research Program of the National Library of Medicine at the National Institutes of Health/DHHS. FAK is an NSF Graduate Fellow. We thank Yuri Pavlov for helpful discussions. author: - first_name: Vladimir full_name: Babenko, Vladimir N last_name: Babenko - first_name: Malay full_name: Basu, Malay K last_name: Basu - first_name: Fyodor full_name: Fyodor Kondrashov id: 44FDEF62-F248-11E8-B48F-1D18A9856A87 last_name: Kondrashov orcid: 0000-0001-8243-4694 - first_name: Igor full_name: Rogozin, Igor B last_name: Rogozin - first_name: Eugene full_name: Koonin, Eugene V last_name: Koonin citation: ama: Babenko V, Basu M, Kondrashov F, Rogozin I, Koonin E. Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis. BMC Cancer. 2006;6. doi:10.1186/1471-2407-6-36 apa: Babenko, V., Basu, M., Kondrashov, F., Rogozin, I., & Koonin, E. (2006). Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis. BMC Cancer. BioMed Central. https://doi.org/10.1186/1471-2407-6-36 chicago: Babenko, Vladimir, Malay Basu, Fyodor Kondrashov, Igor Rogozin, and Eugene Koonin. “Signs of Positive Selection of Somatic Mutations in Human Cancers Detected by EST Sequence Analysis.” BMC Cancer. BioMed Central, 2006. https://doi.org/10.1186/1471-2407-6-36. ieee: V. Babenko, M. Basu, F. Kondrashov, I. Rogozin, and E. Koonin, “Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis,” BMC Cancer, vol. 6. BioMed Central, 2006. ista: Babenko V, Basu M, Kondrashov F, Rogozin I, Koonin E. 2006. Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis. BMC Cancer. 6. mla: Babenko, Vladimir, et al. “Signs of Positive Selection of Somatic Mutations in Human Cancers Detected by EST Sequence Analysis.” BMC Cancer, vol. 6, BioMed Central, 2006, doi:10.1186/1471-2407-6-36. short: V. Babenko, M. Basu, F. Kondrashov, I. Rogozin, E. Koonin, BMC Cancer 6 (2006). date_created: 2018-12-11T11:49:07Z date_published: 2006-02-09T00:00:00Z date_updated: 2021-01-12T08:21:47Z day: '09' doi: 10.1186/1471-2407-6-36 extern: 1 intvolume: ' 6' license: https://creativecommons.org/licenses/by/4.0/ month: '02' publication: BMC Cancer publication_status: published publisher: BioMed Central publist_id: '6744' quality_controlled: 0 status: public title: Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article volume: 6 year: '2006' ...