Carlo Maria I, Chaim Joshua, Patil Sujata, Kemel Yelena, Schram Alison M, Woo Kaitlin, Coskey Devyn, Nanjangud Gouri J, Voss Martin H, Feldman Darren R, Hsieh James J, Hakimi A Ari, Chen Ying-Bei, Motzer Robert J, Lee Chung-Han
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY.
Clin Genitourin Cancer. 2017 Dec;15(6):e987-e994. doi: 10.1016/j.clgc.2017.04.012. Epub 2017 Apr 26.
Renal medullary carcinoma (RMC) is a rare and aggressive type of kidney cancer that primarily affects young adults with sickle cell trait; outcomes are poor despite treatment. Identifying molecular features of this tumor could provide biologic rationale for novel targeted therapies. The objective was to report on clinical outcomes with systemic therapy and characterize molecular features.
This was a retrospective analysis on 36 patients given a pathologic diagnosis of RMC at one institution from 1995 to 2015. Tumors were analyzed for expression of SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1 (SMARCB1) through immunohistochemistry and for genomic alterations with fluorescence in situ hybridization for SMARCB1, and targeted next-generation sequencing. Time from initiation of therapy to progression of disease and overall survival were calculated using the Kaplan-Meier method.
The median age in the cohort was 28 (range, 12-72) years, and all patients tested had sickle cell trait. Overall survival was 5.8 months (95% confidence interval [CI], 4.1-10.9) and for 12 patients who received platinum-based therapy, median progression-free survival was 2.5 months (95% CI, 1.2-not reached). A total of 10 available tumors underwent analysis with fluorescence in situ hybridization for SMARCB1; this revealed loss of heterozygosity with concurrent translocation in 8, and biallelic loss in 2. Next-generation targeted sequencing showed no recurring mutations.
Outcome was generally poor in this cohort of patients with RMC. Uniform loss of SMARCB1 is a key molecular feature in this tumor and mechanism of loss appears to be mostly through translocations and deletions.
肾髓质癌（RMC）是一种罕见且侵袭性强的肾癌类型，主要影响具有镰状细胞特征的年轻成年人；尽管接受了治疗，但其预后仍很差。确定该肿瘤的分子特征可为新型靶向治疗提供生物学依据。目的是报告全身治疗的临床结果并描述分子特征。
这是一项对1995年至2015年在一家机构被病理诊断为RMC的36例患者的回顾性分析。通过免疫组织化学分析肿瘤中SWI/SNF相关、基质相关、肌动蛋白依赖性染色质调节因子B亚家族成员1（SMARCB1）的表达，并通过荧光原位杂交检测SMARCB1的基因组改变以及进行靶向二代测序。使用Kaplan-Meier方法计算从治疗开始到疾病进展的时间和总生存期。
该队列患者的中位年龄为28岁（范围12 - 72岁），所有检测患者均具有镰状细胞特征。总生存期为5.8个月（95%置信区间[CI]，4.1 - 10.9），对于12例接受铂类治疗的患者，中位无进展生存期为2.5个月（95% CI，1.2 - 未达到）。共有10个可用肿瘤进行了SMARCB1的荧光原位杂交分析；结果显示8个肿瘤存在杂合性缺失并伴有同时发生的易位，2个肿瘤存在双等位基因缺失。二代靶向测序未发现复发性突变。
该队列RMC患者的预后总体较差。SMARCB1的一致缺失是该肿瘤的关键分子特征，缺失机制似乎主要是通过易位和缺失。
