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Functional characte...
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Fang, JunNational Cancer Institute, USA
(author)
Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148
- Article/chapterEnglish2017
Publisher, publication year, extent ...
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2017-04-27
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Springer Science and Business Media LLC,2017
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-154588
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-154588URI
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https://doi.org/10.1038/ncomms15034DOI
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https://lup.lub.lu.se/record/fd63e035-620a-4ae4-af20-2275a95a0376URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Jia, Jinping
(author)
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Makowski, Matthew
(author)
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Xu, Mai
(author)
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Wang, Zhaoming
(author)
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Zhang, Tongwu
(author)
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Hoskins, Jason W.
(author)
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Choi, Jiyeon
(author)
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Han, Younghun
(author)
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Zhang, Mingfeng
(author)
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Thomas, Janelle
(author)
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Kovacs, Michael
(author)
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Collins, Irene
(author)
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Dzyadyk, Marta
(author)
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Thompson, Abbey
(author)
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O'Neill, Maura
(author)
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Das, Sudipto
(author)
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Lan, Qi
(author)
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Koster, Roelof
(author)
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Stolzenberg-Solomon, Rachael S.
(author)
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Kraft, Peter
(author)
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Wolpin, Brian M.
(author)
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Jansen, Pascal W. T. C.
(author)
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Olson, Sara
(author)
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McGlynn, Katherine A.
(author)
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Kanetsky, Peter A.
(author)
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Chatterjee, Nilanjan
(author)
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Barrett, Jennifer H.
(author)
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Dunning, Alison M.
(author)
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Taylor, John C.
(author)
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Newton-Bishop, Julia A.
(author)
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Bishop, D. Timothy
(author)
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Andresson, Thorkell
(author)
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Petersen, Gloria M.
(author)
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Amos, Christopher I.
(author)
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Iles, Mark M.
(author)
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Nathanson, Katherine L.
(author)
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Landi, Maria Teresa
(author)
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Vermeulen, Michiel
(author)
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Brown, Kevin M.
(author)
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Amundadottir, Laufey T.National Cancer Institute, USA
(author)
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Sund, MalinUmeå universitet,Institutionen för kirurgisk och perioperativ vetenskap(Swepub:umu)masu0021(author)
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Ingvar, ChristianLund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Melanoma Study Group,Lund University Research Groups(Swepub:lu)kir-cin
(creator_code:cre_t)
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Olsson, HåkanLund University,Lunds universitet,Medicinsk onkologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumörmikromiljö,Institutionen för kliniska vetenskaper, Lund,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Medical oncology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Tumor microenvironment,Department of Clinical Sciences, Lund,Lund Melanoma Study Group,Lund University Research Groups(Swepub:lu)onk-hol
(creator_code:cre_t)
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Jönsson, GöranLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Melanoma Study Group,Lund University Research Groups(Swepub:lu)onk-gjo
(creator_code:cre_t)
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Borg, ÅkeLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups(Swepub:lu)onk-abo
(creator_code:cre_t)
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Harbst, KatjaLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Melanoma Study Group,Lund University Research Groups(Swepub:lu)med-kbn
(creator_code:cre_t)
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Nielsen, KariLund University,Lunds universitet,Kliniska Vetenskaper, Helsingborg,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Clinical Sciences, Helsingborg,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Lund Melanoma Study Group,Lund University Research Groups(Swepub:lu)med-kni
(creator_code:cre_t)
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Zander, Anita SchmidtLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-asc
(creator_code:cre_t)
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National Cancer Institute, USAInstitutionen för kirurgisk och perioperativ vetenskap
(creator_code:org_t)
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GenoMEL Investigators
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In:Nature Communications: Springer Science and Business Media LLC82041-1723
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- By the author/editor
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Fang, Jun
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Jia, Jinping
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Makowski, Matthe ...
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Xu, Mai
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Wang, Zhaoming
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Zhang, Tongwu
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show more...
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Hoskins, Jason W ...
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Choi, Jiyeon
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Han, Younghun
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Zhang, Mingfeng
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Thomas, Janelle
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Kovacs, Michael
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Collins, Irene
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Dzyadyk, Marta
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Thompson, Abbey
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O'Neill, Maura
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Das, Sudipto
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Lan, Qi
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Koster, Roelof
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Stolzenberg-Solo ...
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Kraft, Peter
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Wolpin, Brian M.
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Jansen, Pascal W ...
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Olson, Sara
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McGlynn, Katheri ...
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Kanetsky, Peter ...
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Chatterjee, Nila ...
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Barrett, Jennife ...
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Dunning, Alison ...
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Taylor, John C.
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Newton-Bishop, J ...
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Bishop, D. Timot ...
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Andresson, Thork ...
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Petersen, Gloria ...
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Amos, Christophe ...
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Iles, Mark M.
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Nathanson, Kathe ...
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Landi, Maria Ter ...
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Vermeulen, Michi ...
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Brown, Kevin M.
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Amundadottir, La ...
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Sund, Malin
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Ingvar, Christia ...
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Olsson, Håkan
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Jönsson, Göran
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Borg, Åke
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Nielsen, Kari
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Zander, Anita Sc ...
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Umeå University
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Lund University