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Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors.
Mazrooei, Parisa; Kron, Ken J; Zhu, Yanyun; Zhou, Stanley; Grillo, Giacomo; Mehdi, Tahmid; Ahmed, Musaddeque; Severson, Tesa M; Guilhamon, Paul; Armstrong, Nicholas Sinnott; Huang, Vincent; Yamaguchi, Takafumi N; Fraser, Michael; van der Kwast, Theodorus; Boutros, Paul C; He, Housheng Hansen; Bergman, Andries M; Bristow, Robert G; Zwart, Wilbert; Lupien, Mathieu.
Afiliação
  • 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.
  • Kron KJ; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
  • Zhu Y; Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • 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.
  • Grillo G; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
  • Mehdi T; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
  • Ahmed M; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
  • Severson TM; Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Guilhamon P; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
  • Armstrong NS; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Huang V; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Yamaguchi TN; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Fraser M; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • van der Kwast T; Department of Pathology and Laboratory Medicine, Toronto General Hospital, University Health Network, Toronto, ON M5G 2C4, Canada.
  • 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.
  • 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.
  • Bergman AM; Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Bristow RG; CRUK Manchester Institute and Manchester Cancer Research Centre, University of Manchester, Manchester M20 4GJ, UK.
  • 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 Netherlan
  • 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.
Cancer Cell ; 36(6): 674-689.e6, 2019 12 09.
Article em En | MEDLINE | ID: mdl-31735626
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Regulação Neoplásica da Expressão Gênica / Proteínas de Homeodomínio / Fator 3-alfa Nuclear de Hepatócito Tipo de estudo: Etiology_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Canadá
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Regulação Neoplásica da Expressão Gênica / Proteínas de Homeodomínio / Fator 3-alfa Nuclear de Hepatócito Tipo de estudo: Etiology_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Canadá