Genomic characterization of renal medullary carcinoma and treatment outcomes Journal Article


Authors: Carlo, M. I.; Chaim, J.; Patil, S.; Kemel, Y.; Schram, A. M.; Woo, K.; Coskey, D.; Nanjangud, G. J.; Voss, M. H.; Feldman, D. R.; Hsieh, J. J.; Hakimi, A. A.; Chen, Y. B.; Motzer, R. J.; Lee, C. H.
Article Title: Genomic characterization of renal medullary carcinoma and treatment outcomes
Abstract: Micro-Abstract Renal medullary carcinoma (RMC) is a rare kidney cancer with poor outcomes. We analyzed treatment outcomes in patients with RMC and performed targeted sequencing of tumors to identify unique molecular features. Although responses to platinum-based therapy were found, these were short-lived. There was uniform loss of SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1 (SMARCB1) through translocations and deletions, and further research should go into targeting this pathway. 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. © 2017 Elsevier Inc.
Keywords: immunohistochemistry; adolescent; adult; child; clinical article; controlled study; human tissue; treatment outcome; treatment response; aged; overall survival; bevacizumab; cisplatin; doxorubicin; sunitinib; cancer growth; capecitabine; gemcitabine; paclitaxel; chemotherapy; methotrexate; carboplatin; progression free survival; retrospective study; kidney carcinoma; ifosfamide; vinblastine; temsirolimus; fluorescence in situ hybridization; genomics; chromosome translocation; heterozygosity loss; kidney cancer; chromosome deletion; pemetrexed; everolimus; medullary carcinoma; retrospective analysis; clinical outcome; smarcb1; next generation sequencing; human; male; female; article; swi/snf related matrix associated actin dependent regulator of chromatin subfamily b member 1
Journal Title: Clinical Genitourinary Cancer
Volume: 15
Issue: 6
ISSN: 1558-7673
Publisher: Elsevier Inc.  
Date Published: 2017-12-01
Start Page: e987
End Page: e994
Language: English
DOI: 10.1016/j.clgc.2017.04.012
PROVIDER: scopus
PUBMED: 28558987
PMCID: PMC5771412
DOI/URL:
Notes: Article -- Export Date: 2 January 2018 -- Source: Scopus
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MSK Authors
  1. Sujata Patil
    422 Patil
  2. Joshua Chaim
    21 Chaim
  3. Robert Motzer
    859 Motzer
  4. Darren Richard Feldman
    204 Feldman
  5. Martin Henner Voss
    153 Voss
  6. Yingbei Chen
    262 Chen
  7. James J Hsieh
    121 Hsieh
  8. Alison Michele Schram
    31 Schram
  9. Yelena Kemel
    21 Kemel
  10. Abraham Ari Hakimi
    164 Hakimi
  11. Maria Isabel Carlo
    39 Carlo
  12. Kaitlin Marie Woo
    100 Woo
  13. Chung-Han   Lee
    51 Lee
  14. Devyn Taylor Coskey
    12 Coskey