Please use this identifier to cite or link to this item:
https://hdl.handle.net/2445/157848
Title: | Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148 |
Author: | Fang, Jun Jia, Jinping Makowski, Matthew Xu, Mai Wang, Zhaoming Zhang, Tongwu Hoskins, Jason W. Carrera Álvarez, Cristina PanScan Consortium TRICL Consortium GenoMEL Consortium |
Keywords: | Càncer de pulmó Càncer de pell Càncer de pàncrees Genètica Lung cancer Skin cancer Pancreas cancer Genetics |
Issue Date: | 2-May-2017 |
Publisher: | Nature Publishing Group |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/ncomms15034 |
It is part of: | Nature Communications, 2018, vol. 8, p. 15034 |
URI: | https://hdl.handle.net/2445/157848 |
Related resource: | https://doi.org/10.1038/ncomms15034 |
ISSN: | 2041-1723 |
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 | |
---|---|---|---|---|
691377.pdf | 1.43 MB | Adobe PDF | View/Open | |
correction.pdf | 139.03 kB | Adobe PDF | View/Open |
This item is licensed under a
Creative Commons License