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A pan-cancer analysis of PBAF complex mutations and their association with immunotherapy response

Author

Listed:
  • A. Ari Hakimi

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Kyrollis Attalla

    (Memorial Sloan Kettering Cancer Center)

  • Renzo G. DiNatale

    (Memorial Sloan Kettering Cancer Center)

  • Irina Ostrovnaya

    (Memorial Sloan Kettering Cancer Center)

  • Jessica Flynn

    (Memorial Sloan Kettering Cancer Center)

  • Kyle A. Blum

    (Memorial Sloan Kettering Cancer Center)

  • Yasser Ged

    (Memorial Sloan Kettering Cancer Center)

  • Douglas Hoen

    (Memorial Sloan Kettering Cancer Center)

  • Sviatoslav M. Kendall

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Ed Reznik

    (Memorial Sloan Kettering Cancer Center)

  • Anita Bowman

    (Memorial Sloan Kettering Cancer Center)

  • Jason Hwee

    (Memorial Sloan Kettering Cancer Center)

  • Christopher J. Fong

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Fengshen Kuo

    (Memorial Sloan Kettering Cancer Center)

  • Martin H. Voss

    (Memorial Sloan Kettering Cancer Center)

  • Timothy A. Chan

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Center for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic)

  • Robert J. Motzer

    (Memorial Sloan Kettering Cancer Center)

Abstract

There is conflicting data regarding the role of PBAF complex mutations and response to immune checkpoint blockade (ICB) therapy in clear cell renal cell carcinoma (ccRCC) and other solid tumors. We assess the prevalence of PBAF complex mutations from two large cohorts including the pan-cancer TCGA project (n = 10,359) and the MSK-IMPACT pan-cancer immunotherapy cohort (n = 3700). Across both cohorts, PBAF complex mutations, predominantly PBRM1 mutations, are most common in ccRCC. In multivariate models of ccRCC patients treated with ICB (n = 189), loss-of-function (LOF) mutations in PBRM1 are not associated with overall survival (OS) (HR = 1.24, p = 0.47) or time to treatment failure (HR = 0.85, p = 0.44). In a series of 11 solid tumors (n = 2936), LOF mutations are not associated with improved OS in a stratified multivariate model (HR = 0.9, p = 0.7). In a current series of solid tumors treated with ICB, we are unable to demonstrate favorable response to ICB in patients with PBAF complex mutations.

Suggested Citation

  • A. Ari Hakimi & Kyrollis Attalla & Renzo G. DiNatale & Irina Ostrovnaya & Jessica Flynn & Kyle A. Blum & Yasser Ged & Douglas Hoen & Sviatoslav M. Kendall & Ed Reznik & Anita Bowman & Jason Hwee & Chr, 2020. "A pan-cancer analysis of PBAF complex mutations and their association with immunotherapy response," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17965-0
    DOI: 10.1038/s41467-020-17965-0
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    Cited by:

    1. Li Wang & Jiali Yu & Zishuo Yu & Qianmin Wang & Wanjun Li & Yulei Ren & Zhenguo Chen & Shuang He & Yanhui Xu, 2022. "Structure of nucleosome-bound human PBAF complex," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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