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Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility

Mostra el registre parcial de l'element Solé, Xavier Hernández, Pilar López de Heredia, Miguel de Armengol i Dulcet, Lluís Rodríguez Santiago, Benjamín Gómez, Laia Maxwell, Christopher A. Aguilo, Fernando Condom, Enric Abril, Jesús Pérez Jurado, Luis Alberto Estivill, Xavier, 1955- Nunes, Virginia Capellá, Gabriel Gruber, Stephen B. Moreno, Víctor Pujana, Miguel Angel 2012-05-03T08:26:20Z 2012-05-03T08:26:20Z 2008
dc.identifier.citation Solé X, Hernández P, de Heredia ML, Armengol L, Rodríguez-Santiago B, Gómez L, Maxwell CA, Aguiló F, Condom E, Abril J, Pérez-Jurado L, Estivill X, Nunes V, Capellá G, Gruber SB, Moreno V, Pujana MA. Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility. BMC Genomics. 2008; 9: 12. DOI 10.1186/1471-2164-9-12
dc.identifier.issn 1471-2164
dc.description.abstract Background: Germline genetic variation is associated with the differential expression of many human genes. The phenotypic effects of this type of variation may be important when considering susceptibility to common genetic diseases. Three regions at 8q24 have recently been identified to independently confer risk of prostate cancer. Variation at 8q24 has also recently been associated with risk of breast and colorectal cancer. However, none of the risk variants map at or relatively close to known genes, with c-MYC mapping a few hundred kilobases distally. Results: This study identifies cis-regulators of germline c-MYC expression in immortalized lymphocytes of HapMap individuals. Quantitative analysis of c-MYC expression in normal prostate tissues suggests an association between overexpression and variants in Region 1 of prostate cancer risk. Somatic c-MYC overexpression correlates with prostate cancer progression and more aggressive tumor forms, which was also a pathological variable associated with Region 1. Expression profiling analysis and modeling of transcriptional regulatory networks predicts a functional association between MYC and the prostate tumor suppressor KLF6. Analysis of MYC/Myc-driven cell transformation and tumorigenesis substantiates a model in which MYC overexpression promotes transformation by down-regulating KLF6. In this model, a feedback loop through E-cadherin down-regulation causes further transactivation of c-MYC./nConclusion: This study proposes that variation at putative 8q24 cis-regulator(s) of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene.
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartof BMC Genomics. 2008; 9: 12
dc.rights (c) 2008 Solé et al. Creative Commons Attribution License
dc.subject.other Genètica humana -- Variació
dc.subject.other Genètica molecular
dc.subject.other Càncer -- Aspectes genètics
dc.title Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility
dc.type info:eu-repo/semantics/article
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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