PPARG

Overview

PPARG (peroxisome proliferator-activated receptor gamma) encodes a nuclear receptor transcription factor that regulates adipogenesis, glucose metabolism, and inflammation. In bladder cancer, PPARG is focally amplified in a significant fraction of muscle-invasive tumors and is associated with the luminal-papillary molecular subtype. PPARG activation has been proposed as a driver of urothelial carcinoma differentiation.

Alterations observed in the corpus

  • Focal amplification in 17% of muscle-invasive bladder carcinomas; amplification is one of the most frequent focal copy-number gains in the TCGA bladder cohort and is associated with the luminal-papillary subtype PMID:24476821
  • PAX8/PPARG fusion detected in 4/484 (0.8%) papillary thyroid carcinomas (PTCs); PPARG is the 3’ fusion partner; fusion tumors display RAS-like (RL) expression phenotype with concurrent PI3K/AKT/MAPK activation, mutually exclusive with BRAF/RAS/EIF1AX point mutations. PMID:25417114
  • PPARG found as the 3-prime fusion partner of PAX8 in 3 PDTCs in a targeted-sequencing study of advanced thyroid cancers; the PAX8-PPARG fusion recapitulates a rearrangement previously described in follicular thyroid carcinoma. PMID:26878173
  • PPARG has six recurrent fusions in MIBC (4x TSEN2-PPARG, 2x MKRN2-PPARG) with overexpression (p=6e-3); 4/6 retained both DNA- and ligand-binding domains; additional cell-line CASC15-PPARG and NR2C2-PPARG fusions identified; implicated as a luminal driver alongside GATA3 and FOXA1 PMID:28988769

Cancer types (linked)

  • BLCA (Bladder Urothelial Carcinoma): Focal amplification in 17% of muscle-invasive tumors; PPARG pathway activation drives luminal gene expression programs PMID:24476821

Co-occurrence and mutual exclusivity

  • PPARG amplification enriched in the luminal-papillary molecular subtype alongside FGFR3 mutations and ERBB2 alterations.

Therapeutic relevance

  • PPARG agonists (thiazolidinediones) have been explored in bladder cancer models; amplification may predict sensitivity to PPARG pathway modulation.

Open questions

  • Whether PPARG amplification is a bona fide driver of urothelial differentiation or a passenger in an amplicon involving other genes requires further study.

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:25417114

This page was processed by wiki-cli on 2026-05-14. - PMID:26878173

This page was processed by wiki-cli on 2026-05-14. - PMID:28988769

This page was processed by wiki-cli on 2026-05-15.