Comprehensive Molecular Characterization Identifies Distinct Genomic and Immune Hallmarks of Renal Medullary Carcinoma.

Fiche publication

Date publication

avril 2020

Journal

Cancer cell

Auteurs

Membres identifiés du Cancéropôle Est :
Dr DAVIDSON Irwin , Pr MALOUF Gabriel

Tous les auteurs :
Msaouel P, Malouf GG, Su X, Yao H, Tripathi DN, Soeung M, Gao J, Rao P, Coarfa C, Creighton CJ, Bertocchio JP, Kunnimalaiyaan S, Multani AS, Blando J, He R, Shapiro DD, Perelli L, Srinivasan S, Carbone F, Pilié PG, Karki M, Seervai RNH, Vokshi BH, Lopez-Terrada D, Cheng EH, Tang X, Lu W, Wistuba II, Thompson TC, Davidson I, Giuliani V, Schlacher K, Carugo A, Heffernan TP, Sharma P, Karam JA, Wood CG, Walker CL, Genovese G, Tannir NM

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/32359397

Résumé

Renal medullary carcinoma (RMC) is a highly lethal malignancy that mainly afflicts young individuals of African descent and is resistant to all targeted agents used to treat other renal cell carcinomas. Comprehensive genomic and transcriptomic profiling of untreated primary RMC tissues was performed to elucidate the molecular landscape of these tumors. We found that RMC was characterized by high replication stress and an abundance of focal copy-number alterations associated with activation of the stimulator of the cyclic GMP-AMP synthase interferon genes (cGAS-STING) innate immune pathway. Replication stress conferred a therapeutic vulnerability to drugs targeting DNA-damage repair pathways. Elucidation of these previously unknown RMC hallmarks paves the way to new clinical trials for this rare but highly lethal malignancy.