Characterizing recurrent and lethal small renal masses in clear cell renal cell carcinoma using recurrent somatic mutations Journal Article


Authors: Manley, B. J.; Reznik, E.; Ghanaat, M.; Kashan, M.; Becerra, M. F.; Casuscelli, J.; Tennenbaum, D.; Redzematovic, A.; Carlo, M. I.; Sato, Y.; Arcila, M.; Voss, M. H.; Feldman, D. R.; Motzer, R. J.; Russo, P.; Coleman, J.; Hsieh, J. J.; Hakimi, A. A.
Article Title: Characterizing recurrent and lethal small renal masses in clear cell renal cell carcinoma using recurrent somatic mutations
Abstract: Introduction: Small renal masses (SRMs) with evidence of clear cell renal cell carcinoma (ccRCC) are understudied. Current algorithms for the management of SRMs include surgical resection, ablation, and active surveillance. We sought to identify genomic biomarkers that could potentially refine the management of ccRCC in SRMs, especially in patients being evaluated for active surveillance. Methods: We identified patients who had SRMs (4 cm or less) at time of surgery, had sequencing performed on their primary tumor and had a diagnosis of ccRCC. Patients were selected from 3 publicly available cohorts, The Cancer Genome Atlas (n = 110), University of Tokyo (n = 37), The International Cancer Genome Consortium (n = 31), and from our own institutional prospective database (n = 25). Among this cohort we analyzed mutations present in at least 5% of tumors, assessing for the enrichment of mutations and progression-free survival using the composite endpoint of recurrence or death of disease. Analysis was adjusted for multiple testing. A Cox regression model was used to assess clinical variables with significant mutations. Results: In total, 203 patients were available for analysis. Median follow-up was 43.1 months among survivors. Mutations in VHL, PBRM1, SETD2, BAP1, KDM5C, and MTOR were present in more than 5% of tumors. Twenty-three patients (11.3%) had recurrence or died of their disease. Mutations in KDM5C were associated with inferior survival from either recurrence or death from disease, adjusted P 0.033. Conclusions: We identified mutations in SRMs in ccRCC that are associated with recurrence and lethality. The strongest association was seen in those with KDM5C mutations. Use of these genomic biomarkers may improve stratification of patients with SRMs and for those who may be appropriate for active surveillance. Prospective evaluation of these markers is needed. © 2018 Elsevier Inc.
Keywords: adult; cancer survival; controlled study; aged; survival analysis; primary tumor; major clinical study; somatic mutation; cancer recurrence; follow up; prospective study; gene; progression free survival; cohort analysis; genetic association; mutational analysis; kidney carcinoma; cancer mortality; cancer survivor; risk assessment; cancer size; risk stratification; clear cell carcinoma; vhl gene; japan; mutations; bap1 gene; small renal masses; mtor gene; pbrm1 gene; setd2 gene; human; male; female; priority journal; article; kdm5c; genomic biomarkers; kdm5c gene; kidney clear cell carcinoma
Journal Title: Urologic Oncology: Seminars and Original Investigations
Volume: 37
Issue: 1
ISSN: 1078-1439
Publisher: Elsevier Inc.  
Date Published: 2019-01-01
Start Page: 12
End Page: 17
Language: English
DOI: 10.1016/j.urolonc.2017.10.012
PROVIDER: scopus
PMCID: PMC5984192
PUBMED: 29132830
DOI/URL:
Notes: Urol. Oncol. Semin. Orig. Invest. -- Cited By :4 -- Export Date: 2 January 2019 -- Article -- CODEN: UOSOA C2 - 29132830 -- Source: Scopus
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MSK Authors
  1. Robert Motzer
    744 Motzer
  2. Darren Richard Feldman
    171 Feldman
  3. Martin Henner Voss
    126 Voss
  4. James J Hsieh
    114 Hsieh
  5. Maria Eugenia Arcila
    336 Arcila
  6. Maria Isabel Carlo
    22 Carlo