| Literature DB >> 32359397 |
Pavlos Msaouel1, Gabriel G Malouf2, Xiaoping Su3, Hui Yao3, Durga N Tripathi4, Melinda Soeung5, Jianjun Gao6, Priya Rao7, Cristian Coarfa8, Chad J Creighton9, Jean-Philippe Bertocchio10, Selvi Kunnimalaiyaan11, Asha S Multani12, Jorge Blando13, Rong He6, Daniel D Shapiro14, Luigi Perelli6, Sanjana Srinivasan15, Federica Carbone6, Patrick G Pilié6, Menuka Karki4, Riyad N H Seervai16, Bujamin H Vokshi2, Dolores Lopez-Terrada17, Emily H Cheng18, Ximing Tang19, Wei Lu19, Ignacio I Wistuba19, Timothy C Thompson6, Irwin Davidson20, Virginia Giuliani21, Katharina Schlacher11, Alessandro Carugo21, Timothy P Heffernan21, Padmanee Sharma22, Jose A Karam23, Christopher G Wood14, Cheryl L Walker24, Giannicola Genovese25, Nizar M Tannir26.
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.Entities:
Keywords: SMARCB1; cGAS-STING pathway; molecular profiling; renal medullary carcinoma; replication stress
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Year: 2020 PMID： 32359397 PMCID： PMC7288373 DOI： 10.1016/j.ccell.2020.04.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743