---
_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'
...