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Conference Paper: Programmed genetic instability revealed by adaptive evolution of caretaker tumor suppressor genes

TitleProgrammed genetic instability revealed by adaptive evolution of caretaker tumor suppressor genes
Authors
Issue Date2006
Citation
AACR 97th Annual Meeting, Washington, DC, 1–5 April 2006. In Cancer Research, 2006, v. 66 n. 8S, p. 600 Abstract no. 2542 How to Cite?
AbstractHuman tumor suppressor genes (TSGs) can be subclassified either as caretaker genes (CTs) that maintain genetic stability or else as gatekeeper genes (GKs) that regulate programmed cell death. Cancer risk is increased by dysfunction of either CTs or GKs, but the evolutionary significance of these respective TSG subgroups is less clear. Here we show that germline loss of gene function is better tolerated for CTs than for GKs, and that methylation-dependent CT mutation and/or gene silencing is likely to contribute to such functional germline losses. These conclusions are supported by data mining of familial and sporadic human tumor mutations. Ortholog and single nucleotide polymorphism analyses confirm accelerated evolution of CTs compared to GKs, indicating positive selection due to an adaptive advantage for CT transcriptional repression and/or mutation. We propose that age-dependent CT methylation represents a selectable mechanism for programmed genetic instability (PGI) in the germline, and that somatic cell PGI likewise contributes to the age-dependent incidence of human cancer.
Persistent Identifierhttp://hdl.handle.net/10722/101381
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorEpstein, Ren_HK
dc.contributor.authorZhao, Yen_HK
dc.date.accessioned2010-09-25T19:47:20Z-
dc.date.available2010-09-25T19:47:20Z-
dc.date.issued2006en_HK
dc.identifier.citationAACR 97th Annual Meeting, Washington, DC, 1–5 April 2006. In Cancer Research, 2006, v. 66 n. 8S, p. 600 Abstract no. 2542-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/101381-
dc.description.abstractHuman tumor suppressor genes (TSGs) can be subclassified either as caretaker genes (CTs) that maintain genetic stability or else as gatekeeper genes (GKs) that regulate programmed cell death. Cancer risk is increased by dysfunction of either CTs or GKs, but the evolutionary significance of these respective TSG subgroups is less clear. Here we show that germline loss of gene function is better tolerated for CTs than for GKs, and that methylation-dependent CT mutation and/or gene silencing is likely to contribute to such functional germline losses. These conclusions are supported by data mining of familial and sporadic human tumor mutations. Ortholog and single nucleotide polymorphism analyses confirm accelerated evolution of CTs compared to GKs, indicating positive selection due to an adaptive advantage for CT transcriptional repression and/or mutation. We propose that age-dependent CT methylation represents a selectable mechanism for programmed genetic instability (PGI) in the germline, and that somatic cell PGI likewise contributes to the age-dependent incidence of human cancer.-
dc.languageengen_HK
dc.relation.ispartofCancer Researchen_HK
dc.titleProgrammed genetic instability revealed by adaptive evolution of caretaker tumor suppressor genesen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailEpstein, R: repstein@hku.hken_HK
dc.identifier.emailZhao, Y: yzzhao@yahoo.comen_HK
dc.identifier.authorityEpstein, R=rp00501en_HK
dc.identifier.hkuros115215en_HK

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