Recurrent activating mutations of PPARγ associated with luminal bladder tumors

• DOI: 10.1038/s41467-018-08157-y
• Publication Date: 2019-01-10T12:58:12Z
• Authors: Natacha Rochel; Clémentine Krucker; Laure Coutos-Thév...; Judit Osz; Ruiyun Zhang; Elodie Guyon; Wayne Zita; Séverin Vanthong; Oscar Alba Hernandez; Maxime Bourguet; Kays Al Badawy; Florent Dufour; Carole Peluso-Iltis; Syrine Heckler-Beji; Annick Dejaegere; Aurélie Kamoun; Aurélien de Reyniès; Yann Neuzillet; Sandra Rebouissou; Claire Béraud; Hervé Lang; Thierry Massfelder; Yves Allory; Sarah Cianférani; Roland H. Stote; François Radvanyi; Isabelle Bernard-...
• Keywords: Retinoid X receptor

The upregulation of PPARγ/RXRα transcriptional activity has emerged as a key event in luminal bladder tumors. It renders tumor cell growth PPARγ-dependent and modulates the microenvironment to favor escape from immuno-surveillance. activation pathway been linked PPARG gains/amplifications resulting PPARγ overexpression recurrent activating point mutations RXRα. Here, we report that also activate pathway, conferring PPARγ-dependency supporting crucial role cancer. These are found throughout protein-including N-terminal, DNA-binding ligand-binding domains-and most them enhance protein activity. Structure-function studies variants with domain allow identifying structural elements underpin their gain-of-function. Our study reveals genomic alterations lead pro-tumorigenic tumors may open way towards alternative options for treatment.