Comprehensive molecular characterization identifies distinct genomic and immune hallmarks of renal medullary carcinoma Journal Article
| Authors: | Msaouel, P.; Malouf, G. G.; Su, X.; Yao, H.; Tripathi, D. N.; Soeung, M.; Gao, J.; Rao, P.; Coarfa, C.; Creighton, C. J.; Bertocchio, J. P.; Kunnimalaiyaan, S.; Multani, A. S.; Blando, J.; He, R.; Shapiro, D. D.; Perelli, L.; Srinivasan, S.; Carbone, F.; Pilié, P. G.; Karki, M.; Seervai, R. N. H.; Vokshi, B. H.; Lopez-Terrada, D.; Cheng, E. H.; Tang, X.; Lu, W.; Wistuba, I. I.; Thompson, T. C.; Davidson, I.; Giuliani, V.; Schlacher, K.; Carugo, A.; Heffernan, T. P.; Sharma, P.; Karam, J. A.; Wood, C. G.; Walker, C. L.; Genovese, G.; Tannir, N. M. |
| Article Title: | Comprehensive molecular characterization identifies distinct genomic and immune hallmarks of renal medullary carcinoma |
| 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. Msaouel et al. describe the molecular landscape of renal medullary carcinomas (RMC). These tumors harbor SMARCB1 mutations leading to high MYC expression and replicative stress that sensitize RMC cells to PARP inhibitors. cGAS-STING activation in RMCs warrants exploration of immunotherapy for these patients. © 2020 Elsevier Inc. |
| Keywords: | molecular profiling; renal medullary carcinoma; smarcb1; replication stress; cgas-sting pathway |
| Journal Title: | Cancer Cell |
| Volume: | 37 |
| Issue: | 5 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2020-05-11 |
| Start Page: | 720 |
| End Page: | 734.e13 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2020.04.002 |
| PUBMED: | 32359397 |
| PROVIDER: | scopus |
| PMCID: | PMC7288373 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
