AUTHOR=Chen Zuobing , Chen Canping , Li Lin , Zhang Tianfang , Wang Xiaosheng 

TITLE=Pan-Cancer Analysis Reveals That E1A Binding Protein p300 Mutations Increase Genome Instability and Antitumor Immunity

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.729927

DOI=10.3389/fcell.2021.729927

ISSN=2296-634X

ABSTRACT=<p><italic>E1A binding protein p300</italic> (<italic>EP300</italic>) is mutated in diverse cancers. Nevertheless, a systematic investigation into the associations of <italic>EP300</italic> mutations with genome instability and antitumor immunity in pan-cancer remains lacking. Using the datasets from The Cancer Genome Atlas, we analyzed the correlations between <italic>EP300</italic> mutations and genome instability and antitumor immune response in 11 cancer types. Compared to <italic>EP300</italic>-wild-type cancers, <italic>EP300</italic>-mutated cancers had significantly higher tumor mutation burden (TMB) in 10 cancer types. <italic>EP300</italic>-mutated cancers harbored a much higher fraction of microsatellite instable cancers in the colon and gastric cancers. <italic>EP300</italic> was co-mutated with genes involved in DNA damage repair pathways in multiple cancers. Furthermore, compared to <italic>EP300</italic>-wild-type cancers, <italic>EP300</italic>-mutated cancers had significantly higher immune cytolytic activity scores and ratios of immune-stimulatory over immune-inhibitory signatures in diverse cancers. Also, <italic>EP300</italic>-mutated cancers showed significantly higher programmed death-ligand 1 (<italic>PD-L1</italic>) expression levels than <italic>EP300</italic>-wild-type cancers. The increased TMB, antitumor immune activity, and PD-L1 expression indicated a favorable response to immune checkpoint inhibitors (ICIs) in <italic>EP300</italic>-mutated cancers, as evident in three cancer cohorts treated with ICIs. Thus, the <italic>EP300</italic> mutation could be a predictive biomarker for the response to immunotherapy.</p>