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Inflammation-Induced Oxidative Stress Mediates Gene Fusion Formation in Prostate Cancer.
Mani, Ram S; Amin, Mohammad A; Li, Xiangyi; Kalyana-Sundaram, Shanker; Veeneman, Brendan A; Wang, Lei; Ghosh, Aparna; Aslam, Adam; Ramanand, Susmita G; Rabquer, Bradley J; Kimura, Wataru; Tran, Maxwell; Cao, Xuhong; Roychowdhury, Sameek; Dhanasekaran, Saravana M; Palanisamy, Nallasivam; Sadek, Hesham A; Kapur, Payal; Koch, Alisa E; Chinnaiyan, Arul M.
Afiliação
  • Mani RS; Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75235, USA; Department of Urology, UT Southwestern Medical Center, Dallas, TX 75235, USA; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75235, USA. Electronic address: ram.mani@utsouthwest
  • Amin MA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Li X; Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75235, USA.
  • Kalyana-Sundaram S; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Veeneman BA; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109
  • Wang L; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Ghosh A; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Aslam A; Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75235, USA.
  • Ramanand SG; Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75235, USA.
  • Rabquer BJ; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Kimura W; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75235, USA; Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8577, Japan.
  • Tran M; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Cao X; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Roychowdhury S; Department of Internal Medicine, The James Cancer Center, Ohio State University, Columbus, OH 43210, USA.
  • Dhanasekaran SM; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Palanisamy N; Department of Urology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Sadek HA; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75235, USA.
  • Kapur P; Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75235, USA; Department of Urology, UT Southwestern Medical Center, Dallas, TX 75235, USA.
  • Koch AE; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA; VA Ann Arbor, Ann Arbor, MI 48105, USA.
  • Chinnaiyan AM; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109
Cell Rep ; 17(10): 2620-2631, 2016 12 06.
Article em En | MEDLINE | ID: mdl-27926866
ABSTRACT
Approximately 50% of prostate cancers are associated with gene fusions of the androgen-regulated gene TMPRSS2 to the oncogenic erythroblast transformation-specific (ETS) transcription factor ERG. The three-dimensional proximity of TMPRSS2 and ERG genes, in combination with DNA breaks, facilitates the formation of TMPRSS2-ERG gene fusions. However, the origins of DNA breaks that underlie gene fusion formation in prostate cancers are far from clear. We demonstrate a role for inflammation-induced oxidative stress in the formation of DNA breaks leading to recurrent TMPRSS2-ERG gene fusions. The transcriptional status and epigenetic features of the target genes influence this effect. Importantly, inflammation-induced de novo genomic rearrangements are blocked by homologous recombination (HR) and promoted by non-homologous end-joining (NHEJ) pathways. In conjunction with the association of proliferative inflammatory atrophy (PIA) with human prostate cancer, our results support a working model in which recurrent genomic rearrangements induced by inflammatory stimuli lead to the development of prostate cancer.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Serina Endopeptidases / Proteínas de Fusão Oncogênica / Inflamação Tipo de estudo: Prognostic_studies Limite: Humans / Male Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Serina Endopeptidases / Proteínas de Fusão Oncogênica / Inflamação Tipo de estudo: Prognostic_studies Limite: Humans / Male Idioma: En Ano de publicação: 2016 Tipo de documento: Article