Genomic alterations as predictors of survival among patients within a combined cohort with clear cell renal cell carcinoma undergoing cytoreductive nephrectomy Journal Article


Authors: Tennenbaum, D. M.; Manley, B. J.; Zabor, E.; Becerra, M. F.; Carlo, M. I.; Casuscelli, J.; Redzematovic, A.; Khan, N.; Arcila, M. E.; Voss, M. H.; Feldman, D. R.; Motzer, R. J.; Benfante, N. E.; Coleman, J. A.; Russo, P.; Hsieh, J. J.; Hakimi, A. A.
Article Title: Genomic alterations as predictors of survival among patients within a combined cohort with clear cell renal cell carcinoma undergoing cytoreductive nephrectomy
Abstract: Purpose To establish prognostic genomic biomarkers for patients with metastatic clear cell renal cell carcinoma (ccRCC). Materials and methods We identified 60 patients who presented with metastatic ccRCC at our institution between 2001 and 2015 and had genomic sequencing on their primary tumor. We pooled these patients with 107 other patients with the same inclusion criteria from three well-known public databases. Five commonly mutated genes were chosen for analysis: VHL, PBRM1, BAP1, SETD2, and KDM5C. Overall survival (OS) was estimated using the Kaplan-Meier method and the log-rank test was used for comparisons between groups. Results Median OS in the cohort was 2.5 years. Higher Fuhrman grade was associated with decreased median OS (P<0.001). Mutations in SETD2 (P = 0.027) and KDM5C (P = 0.019) were associated with reduced risk of death (hazard ratio [HR] = 0.58 [95% CI: 0.35–0.94] and HR = 0.43 [95% CI: 0.22–0.85], respectively). BAP1 mutations (P = 0.008) were associated with increased risk of death (HR = 1.81 [95% CI: 1.16–2.83]). There were significantly more female patients with a BAP1 mutation than females in the overall cohort (P = 0.001). Conclusions Mutations in BAP1 negatively affected OS, whereas SETD2 and KDM5C mutations were associated with prolonged OS in our pooled cohort of 167 patients with metastatic ccRCC. Our results expand upon efforts at understanding genomic biomarkers in localized disease. Those efforts set the stage for our novel investigation examining associations of select recurrent somatic mutations in stage IV patients with ccRCC. © 2017 Elsevier Inc.
Keywords: mortality; renal cell carcinoma; neoplasm metastasis; prognosis
Journal Title: Urologic Oncology: Seminars and Original Investigations
Volume: 35
Issue: 8
ISSN: 1078-1439
Publisher: Elsevier Inc.  
Date Published: 2017-08-01
Start Page: 532.e7
End Page: 532.e13
Language: English
DOI: 10.1016/j.urolonc.2017.03.015
PROVIDER: scopus
PMCID: PMC5545055
PUBMED: 28408295
DOI/URL:
Notes: Article -- Export Date: 1 September 2017 -- Source: Scopus
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MSK Authors
  1. Jonathan Coleman
    181 Coleman
  2. Paul Russo
    443 Russo
  3. Robert Motzer
    707 Motzer
  4. Darren Richard Feldman
    164 Feldman
  5. Martin Henner Voss
    122 Voss
  6. Emily Craig Zabor
    119 Zabor
  7. James J Hsieh
    114 Hsieh
  8. Maria Eugenia Arcila
    328 Arcila
  9. Abraham Ari Hakimi
    127 Hakimi
  10. Maria Isabel Carlo
    21 Carlo
  11. Brandon John Manley
    21 Manley
  12. Maria Fernanda   Becerra
    15 Becerra
  13. Nabeela Ali Khan
    2 Khan