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

Cancer Cell
Authors
Keywords
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.

Year of Publication
2014
Journal
Cancer Cell
Volume
25
Issue
6
Pages
762-77
Date Published
2014 Jun 16
ISSN
1878-3686
URL
DOI
10.1016/j.ccr.2014.04.024
PubMed ID
24937458
PubMed Central ID
PMC4079039
Links
Grant list
P01 CA080111 / CA / NCI NIH HHS / United States
R01 GM099409 / GM / NIGMS NIH HHS / United States
CA080111 / CA / NCI NIH HHS / United States
GM099409 / GM / NIGMS NIH HHS / United States