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Transcriptomes of Prostate Cancer with TMPRSS2:ERG and Other ETS Fusions.
Stopsack, Konrad H; Su, Xiaofeng A; Vaselkiv, J Bailey; Graff, Rebecca E; Ebot, Ericka M; Pettersson, Andreas; Lis, Rosina T; Fiorentino, Michelangelo; Loda, Massimo; Penney, Kathryn L; Lotan, Tamara L; Mucci, Lorelei A.
Afiliação
  • Stopsack KH; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • Su XA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Vaselkiv JB; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • Graff RE; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
  • Ebot EM; Division of Research, Kaiser Permanente Northern California, Oakland, California.
  • Pettersson A; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California.
  • Lis RT; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • Fiorentino M; Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
  • Loda M; Department of Pathology and Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Penney KL; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • Lotan TL; Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Bologna, Italy.
  • Mucci LA; Department of Pathology, Weill Cornell Medical College, New York, New York.
Mol Cancer Res ; 21(1): 14-23, 2023 01 03.
Article em En | MEDLINE | ID: mdl-36125519
ABSTRACT
The most common somatic event in primary prostate cancer is a fusion between the androgen-related TMPRSS2 gene and the ERG oncogene. Tumors with these fusions, which occur early in carcinogenesis, have a distinctive etiology. A smaller subset of other tumors harbor fusions between TMPRSS2 and members of the ETS transcription factor family other than ERG. To assess the genomic similarity of tumors with non-ERG ETS fusions and those with fusions involving ERG, this study derived a transcriptomic signature of non-ERG ETS fusions and assessed this signature and ERG-related gene expression in 1,050 men with primary prostate cancer from three independent population-based and hospital-based studies. Although non-ERG ETS fusions involving ETV1, ETV4, ETV5, or FLI1 were individually rare, they jointly accounted for one in seven prostate tumors. Genes differentially regulated between non-ERG ETS tumors and tumors without ETS fusions showed similar differential expression when ERG tumors and tumors without ETS fusions were compared (differences explained R2 = 69-77%), including ETS-related androgen receptor (AR) target genes. Differences appeared to result from similarities among ETS tumors rather than similarities among non-ETS tumors. Gene sets associated with ERG fusions were consistent with gene sets associated with non-ERG ETS fusions, including fatty acid and amino acid metabolism, an observation that was robust across cohorts. IMPLICATIONS Considering ETS fusions jointly may be useful for etiologic studies on prostate cancer, given that the transcriptome is profoundly impacted by ERG and non-ERG ETS fusions in a largely similar fashion, most notably genes regulating metabolic pathways.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Transcriptoma Limite: Humans / Male Idioma: En Revista: Mol Cancer Res Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Transcriptoma Limite: Humans / Male Idioma: En Revista: Mol Cancer Res Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article