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

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

Cancer cell (2020-05-04)

Pavlos Msaouel, Gabriel G Malouf, Xiaoping Su, Hui Yao, Durga N Tripathi, Melinda Soeung, Jianjun Gao, Priya Rao, Cristian Coarfa, Chad J Creighton, Jean-Philippe Bertocchio, Selvi Kunnimalaiyaan, Asha S Multani, Jorge Blando, Rong He, Daniel D Shapiro, Luigi Perelli, Sanjana Srinivasan, Federica Carbone, Patrick G Pilié, Menuka Karki, Riyad N H Seervai, Bujamin H Vokshi, Dolores Lopez-Terrada, Emily H Cheng, Ximing Tang, Wei Lu, Ignacio I Wistuba, Timothy C Thompson, Irwin Davidson, Virginia Giuliani, Katharina Schlacher, Alessandro Carugo, Timothy P Heffernan, Padmanee Sharma, Jose A Karam, Christopher G Wood, Cheryl L Walker, Giannicola Genovese, Nizar M Tannir

PMID32359397

ABSTRACT

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.

MATERIALS

Product Number

Brand

Product Description

SAB4200202

Sigma-Aldrich

Anti- INI1/SNF5 antibody, Mouse monoclonal, clone 2C2, purified from hybridoma cell culture