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.
Cancer Cell. 2020 May 11;37(5):720-734.e13. doi: 10.1016/j.ccell.2020.04.002. Epub 2020 Apr 30.
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.
肾髓质癌（RMC）是一种高度致命的恶性肿瘤，主要影响非洲裔年轻个体，对所有用于治疗其他肾细胞癌的靶向药物均具有耐药性。对未经治疗的原发性 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特征。我们发现 RMC 的特点是高复制应激和大量与环鸟苷酸-腺苷酸合酶干扰素基因（cGAS-STING）先天免疫途径激活相关的局灶性拷贝数改变。复制应激使针对 DNA 损伤修复途径的药物具有治疗易感性。阐明这些以前未知的 RMC 特征为这种罕见但高度致命的恶性肿瘤开辟了新的临床试验途径。
