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

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Comprehensive Molecular Characterization Identifies Distinct Genomic and Immune Hallmarks of Renal Medullary Carcinoma.
Cancer Cell ( IF 50.3 ) Pub Date : 2020-04-30 , DOI: 10.1016/j.ccell.2020.04.002
Pavlos Msaouel ₁ , Gabriel G Malouf ₂ , Xiaoping Su ₃ , Hui Yao ₃ , Durga N Tripathi ₄ , Melinda Soeung ₅ , Jianjun Gao ₆ , Priya Rao ₇ , Cristian Coarfa ₈ , Chad J Creighton ₉ , Jean-Philippe Bertocchio ₁ , Selvi Kunnimalaiyaan ₁₀ , Asha S Multani ₁₁ , Jorge Blando ₁₂ , Rong He ₆ , Daniel D Shapiro ₁₃ , Luigi Perelli ₆ , Sanjana Srinivasan ₁₄ , Federica Carbone ₆ , Patrick G Pilié ₆ , Menuka Karki ₄ , Riyad N H Seervai ₁₅ , Bujamin H Vokshi ₂ , Dolores Lopez-Terrada ₁₆ , Emily H Cheng ₁₇ , Ximing Tang ₁₈ , Wei Lu ₁₈ , Ignacio I Wistuba ₁₈ , Timothy C Thompson ₆ , Irwin Davidson ₁₉ , Virginia Giuliani ₂₀ , Katharina Schlacher ₁₀ , Alessandro Carugo ₂₀ , Timothy P Heffernan ₂₀ , Padmanee Sharma ₂₁ , Jose A Karam ₂₂ , Christopher G Wood ₁₃ , Cheryl L Walker ₂₃ , Giannicola Genovese ₂₄ , Nizar M Tannir ₆

Affiliation

Department of Genitourinary Medical Oncology, Unit 1374, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Houston, TX 77030-3721, USA; Center for Precision Environmental Health, Baylor College of Medicine, Houston, Texas, USA.
Department of Hematology and Oncology, Strasbourg University Hospitals, Strasbourg University, Strasbourg, France; Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UNISTRA, Illkirch Cedex, France.
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Center for Precision Environmental Health, Baylor College of Medicine, Houston, Texas, USA.
Department of Genomic Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Department of Genitourinary Medical Oncology, Unit 1374, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Houston, TX 77030-3721, USA.
Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Department of Genomic Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Center for Precision Environmental Health, Baylor College of Medicine, Houston, Texas, USA; Molecular & Cellular Biology Graduate Program, Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Pathology, Texas Children's Hospital, Houston, TX 77030, USA.
Human Oncology & Pathogenesis Program and Department of Pathology, Memorial Sloan Kettering Cancer Institute, New York City, NY 10065, USA.
Department of Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UNISTRA, Illkirch Cedex, France.
Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION), The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Genitourinary Medical Oncology, Unit 1374, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Houston, TX 77030-3721, USA; Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Center for Precision Environmental Health, Baylor College of Medicine, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Department of Medicine, Baylor College of Medicine, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Department of Genitourinary Medical Oncology, Unit 1374, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Houston, TX 77030-3721, USA; Department of Genomic Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

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.

中文翻译：

全面的分子表征可识别肾髓样癌的不同基因组和免疫标志。

肾髓样癌 (RMC) 是一种高度致命的恶性肿瘤，主要影响非洲裔年轻人，并且对用于治疗其他肾细胞癌的所有靶向药物具有耐药性。对未经处理的原发性 RMC 组织进行了全面的基因组和转录组分析，以阐明这些肿瘤的分子景观。我们发现 RMC 的特征是高复制压力和大量与激活环状 GMP-AMP 合酶干扰素基因 (cGAS-STING) 先天免疫途径的刺激物相关的局灶拷贝数改变。复制压力赋予了针对 DNA 损伤修复途径的药物的治疗脆弱性。阐明这些以前未知的 RMC 标志为这种罕见但高度致命的恶性肿瘤的新临床试验铺平了道路。

更新日期：2020-04-30

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