Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cancer Cell. 2014 Jun 16;25(6):762-77. doi: 10.1016/j.ccr.2014.04.024.

JARID1B is a luminal lineage-driving oncogene in breast cancer.

Author information

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  • 2Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard School of Public Health, Boston, MA 02115, USA.
  • 3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Oslo University Hospital, Radiumhospitalet, Oslo 0310, Norway.
  • 4Five3 Genomics, Santa Cruz, CA 95060, USA.
  • 5Stanford Center for Cancer Systems Biology, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 6Oslo University Hospital, Radiumhospitalet, Oslo 0310, Norway.
  • 7Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; School of Medicine, Sapporo Medical University, Sapporo 060-8556, Japan.
  • 8Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
  • 9Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-799, Korea.
  • 10Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; San Raffaele University, 20132 Milan, Italy.
  • 11Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
  • 12Thomson Reuters Healthcare & Science, Encinitas, CA 92024, USA.
  • 13Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • 14Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard School of Public Health, Boston, MA 02115, USA; Broad Institute, Cambridge, MA 02141, USA.
  • 15Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Broad Institute, Cambridge, MA 02141, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: kornelia_polyak@dfci.harvard.edu.

Abstract

Recurrent mutations in histone-modifying enzymes imply key roles in tumorigenesis, yet their functional relevance is largely unknown. Here, we show that JARID1B, encoding a histone H3 lysine 4 (H3K4) demethylase, is frequently amplified and overexpressed in luminal breast tumors and a somatic mutation in a basal-like breast cancer results in the gain of unique chromatin binding and luminal expression and splicing patterns. Downregulation of JARID1B in luminal cells induces basal genes expression and growth arrest, which is rescued by TGFβ pathway inhibitors. Integrated JARID1B chromatin binding, H3K4 methylation, and expression profiles suggest a key function for JARID1B in luminal cell-specific expression programs. High luminal JARID1B activity is associated with poor outcome in patients with hormone receptor-positive breast tumors.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID:
24937458
[PubMed - indexed for MEDLINE]
PMCID:
PMC4079039
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk