Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors.

Cell Line, Tumor Gene Expression Regulation, Neoplastic / genetics Hepatocyte Nuclear Factor 3-alpha / metabolism Homeodomain Proteins / genetics Humans Male Mutation / genetics Prostatic Neoplasms / metabolism Up-Regulation / genetics
H3K27ac accessible chromatin cis-regulatory elements epigenetics noncoding mutations prostate cancer prostate tumor risk SNP single-nucleotide variant transcription factors transcription regulators

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
09 12 2019
Historique:
received: 14 08 2018
revised: 02 08 2019
accepted: 17 10 2019
pubmed: 19 11 2019
medline: 28 5 2020
entrez: 19 11 2019
Statut: ppublish

Résumé

Thousands of noncoding somatic single-nucleotide variants (SNVs) of unknown function are reported in tumors. Partitioning the genome according to cistromes reveals the enrichment of somatic SNVs in prostate tumors as opposed to adjacent normal tissue cistromes of master transcription regulators, including AR, FOXA1, and HOXB13. This parallels enrichment of prostate cancer genetic predispositions over these transcription regulators' tumor cistromes, exemplified at the 8q24 locus harboring both risk variants and somatic SNVs in cis-regulatory elements upregulating MYC expression. However, Massively Parallel Reporter Assays reveal that few SNVs can alter the transactivation potential of individual cis-regulatory elements. Instead, similar to inherited risk variants, SNVs accumulate in cistromes of master transcription regulators required for prostate cancer development.

Identifiants

DOI: 10.1016/j.ccell.2019.10.005 PMID: 31735626
pubmed: 31735626
pii: S1535-6108(19)30479-9
doi: 10.1016/j.ccell.2019.10.005
pii:
doi:

Substances chimiques

HOXB13 protein, human 0
Hepatocyte Nuclear Factor 3-alpha 0
Homeodomain Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

674-689.e6

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Parisa Mazrooei (P)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.

Ken J Kron (KJ)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.

Yanyun Zhu (Y)

Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, The Netherlands.

Stanley Zhou (S)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.

Giacomo Grillo (G)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.

Tahmid Mehdi (T)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.

Musaddeque Ahmed (M)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.

Tesa M Severson (TM)

Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, The Netherlands.

Paul Guilhamon (P)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.

Nicholas Sinnott Armstrong (NS)

Department of Genetics, Stanford University, Stanford, CA 94305, USA.

Vincent Huang (V)

Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.

Takafumi N Yamaguchi (TN)

Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.

Michael Fraser (M)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.

Theodorus van der Kwast (T)

Department of Pathology and Laboratory Medicine, Toronto General Hospital, University Health Network, Toronto, ON M5G 2C4, Canada.

Paul C Boutros (PC)

Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Housheng Hansen He (HH)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.

Andries M Bergman (AM)

Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, The Netherlands.

Robert G Bristow (RG)

CRUK Manchester Institute and Manchester Cancer Research Centre, University of Manchester, Manchester M20 4GJ, UK.

Wilbert Zwart (W)

Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, The Netherlands; Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands. Electronic address: w.zwart@nki.nl.

Mathieu Lupien (M)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada. Electronic address: mlupien@uhnres.utoronto.ca.

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Cistrome Partitioning Reveals Convergence of...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Cistrome Partitioning Reveals Convergence of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif hélice ailée › Facteurs de transcription Forkhead › Facteur nucléaire hépatocytaire HNF-3 alpha › Cistrome Partitioning Reveals Convergence of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de liaison à l'ADN › Protéines à homéodomaine › Cistrome Partitioning Reveals Convergence of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Cistrome Partitioning Reveals Convergence of...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Cistrome Partitioning Reveals Convergence of...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Cistrome Partitioning Reveals Convergence of...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation positive › Cistrome Partitioning Reveals Convergence of...