1. Comprehensive Molecular Characterization Identifies Distinct Genomic and Immune Hallmarks of Renal Medullary Carcinoma.
- Author
-
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, and Tannir NM
- Subjects
- Adult, Animals, Apoptosis, Biomarkers, Tumor genetics, Carcinoma, Medullary genetics, Carcinoma, Medullary immunology, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell immunology, Cell Proliferation, Cohort Studies, DNA Copy Number Variations, Female, Gene Expression Regulation, Neoplastic, Genomics, High-Throughput Nucleotide Sequencing, Humans, Kidney Neoplasms genetics, Kidney Neoplasms immunology, Male, Membrane Proteins genetics, Membrane Proteins metabolism, Mice, Mice, Nude, Nucleotidyltransferases genetics, Nucleotidyltransferases metabolism, Prognosis, Proto-Oncogene Proteins c-myc genetics, Proto-Oncogene Proteins c-myc metabolism, SMARCB1 Protein genetics, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Biomarkers, Tumor metabolism, Carcinoma, Medullary pathology, Carcinoma, Renal Cell pathology, Chromosome Aberrations, DNA Replication, Kidney Neoplasms pathology, SMARCB1 Protein metabolism
- 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., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF