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http://hdl.handle.net/2445/157848
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DC Field | Value | Language |
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dc.contributor.author | Fang, Jun | - |
dc.contributor.author | Jia, Jinping | - |
dc.contributor.author | Makowski, Matthew | - |
dc.contributor.author | Xu, Mai | - |
dc.contributor.author | Wang, Zhaoming | - |
dc.contributor.author | Zhang, Tongwu | - |
dc.contributor.author | Hoskins, Jason W. | - |
dc.contributor.author | Carrera Álvarez, Cristina | - |
dc.contributor.author | PanScan Consortium | - |
dc.contributor.author | TRICL Consortium | - |
dc.contributor.author | GenoMEL Consortium | - |
dc.date.accessioned | 2020-04-28T16:34:16Z | - |
dc.date.available | 2020-04-28T16:34:16Z | - |
dc.date.issued | 2017-05-02 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/2445/157848 | - |
dc.description.abstract | Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele. | - |
dc.format.extent | 15 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1038/ncomms15034 | - |
dc.relation.ispartof | Nature Communications, 2018, vol. 8, p. 15034 | - |
dc.relation.uri | https://doi.org/10.1038/ncomms15034 | - |
dc.rights | cc-by (c) Fang, Jun et al., 2018 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Medicina) | - |
dc.subject.classification | Càncer de pulmó | - |
dc.subject.classification | Càncer de pell | - |
dc.subject.classification | Càncer de pàncrees | - |
dc.subject.classification | Genètica | - |
dc.subject.other | Lung cancer | - |
dc.subject.other | Skin cancer | - |
dc.subject.other | Pancreas cancer | - |
dc.subject.other | Genetics | - |
dc.title | Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 691377 | - |
dc.date.updated | 2020-04-28T16:34:16Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/607142/EU//DEVCOM | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 28447668 | - |
Appears in Collections: | Articles publicats en revistes (Medicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Publicacions de projectes de recerca finançats per la UE |
Files in This Item:
File | Description | Size | Format | |
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691377.pdf | 1.43 MB | Adobe PDF | View/Open | |
correction.pdf | 139.03 kB | Adobe PDF | View/Open |
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