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Updated: Mar 1, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Genomic Characterization of Renal Medullary Carcinoma and Treatment Outcomes
Maria I Carlo1, Joshua Chaim2, Sujata Patil3
1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Background:
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.
Patients And Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Renal medullary carcinoma (RMC), a rare kidney cancer in sickle cell trait patients, shows poor outcomes. Uniform loss of SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) is a key molecular feature.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Renal medullary carcinoma (RMC) is an aggressive kidney cancer primarily affecting young adults with sickle cell trait.
- Clinical outcomes for RMC are generally poor despite available treatments.
- Understanding RMC's molecular characteristics is crucial for developing targeted therapies.
Purpose of the Study:
- To report on the clinical outcomes of patients with RMC treated with systemic therapy.
- To characterize the molecular features of RMC tumors.
- To identify potential therapeutic targets based on molecular findings.
Main Methods:
- Retrospective analysis of 36 RMC patients diagnosed between 1995 and 2015.
- Immunohistochemistry and fluorescence in situ hybridization (FISH) to assess SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1 (SMARCB1) expression and alterations.
- Targeted next-generation sequencing (NGS) to identify genomic mutations.
- Kaplan-Meier method to calculate progression-free and overall survival.
Main Results:
- The median age of RMC patients was 28 years, and all had sickle cell trait.
- Overall survival was 5.8 months; median progression-free survival for platinum-based therapy was 2.5 months.
- FISH analysis revealed loss of SMARCB1 in 10 tumors, primarily through translocations and deletions.
- NGS did not identify recurring mutations in the analyzed genes.
Conclusions:
- RMC patient outcomes remain poor, highlighting the need for improved treatments.
- Uniform loss of SMARCB1, often due to translocations and deletions, is a defining molecular characteristic of RMC.
- Further research into SMARCB1's role could lead to novel therapeutic strategies for RMC.
