Abstract
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.
Keywords
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Article info
Publication history
Published online: April 25, 2017
Accepted:
April 14,
2017
Received in revised form:
April 13,
2017
Received:
March 10,
2017
Identification
Copyright
© 2017 Elsevier Inc. All rights reserved.
