TY - JOUR
T1 - A pan-cancer analysis of PBAF complex mutations and their association with immunotherapy response
AU - Hakimi, A. Ari
AU - Attalla, Kyrollis
AU - DiNatale, Renzo G.
AU - Ostrovnaya, Irina
AU - Flynn, Jessica
AU - Blum, Kyle A.
AU - Ged, Yasser
AU - Hoen, Douglas
AU - Kendall, Sviatoslav M.
AU - Reznik, Ed
AU - Bowman, Anita
AU - Hwee, Jason
AU - Fong, Christopher J.
AU - Kuo, Fengshen
AU - Voss, Martin H.
AU - Chan, Timothy A.
AU - Motzer, Robert J.
N1 - Funding Information:
We express our deep gratitude to our patients, their families, and their caregivers. We acknowledge support from the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute (P30CA008748), the Weiss family funds, and the Ruth L. Kirschstein National Research Service Award (T32CA082088).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-020-17965-0
DO - 10.1038/s41467-020-17965-0
M3 - Article
C2 - 32820162
AN - SCOPUS:85089658376
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4168
ER -