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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-08-20

AUTHORS

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, Christopher J. Fong, Fengshen Kuo, Martin H. Voss, Timothy A. Chan, Robert J. Motzer

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. More... »

PAGES

4168

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-020-17965-0

DOI

http://dx.doi.org/10.1038/s41467-020-17965-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1130215141

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32820162


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26 schema:description 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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