Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas.

Campbell, Joshua D; Yau, Christina; Bowlby, Reanne; Liu, Yuexin; Brennan, Kevin; Fan, Huihui; Taylor, Alison M; Wang, Chen; Walter, Vonn; Akbani, Rehan; Byers, Lauren Averett; Creighton, Chad J; Coarfa, Cristian; Shih, Juliann; Cherniack, Andrew D; Gevaert, Olivier; Prunello, Marcos; Shen, Hui; Anur, Pavana; Chen, Jianhong; ... (2018). Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas. Cell reports, 23(1), 194-212.e6. Cell Press 10.1016/j.celrep.2018.03.063

	Text nihms958981.pdf - Accepted Version Restricted to registered users only Available under License Publisher holds Copyright. Download (1MB)
Preview	Text 1-s2.0-S2211124718304248-main.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (8MB) | Preview

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation. Low-CNA SCCs tended to be HPV(+) and display hypermethylation with repression of TET1 demethylase and FANCF, previously linked to predisposition to SCC, or harbor mutations affecting CASP8, RAS-MAPK pathways, chromatin modifiers, and immunoregulatory molecules. We uncovered hypomethylation of the alternative promoter that drives expression of the ΔNp63 oncogene and embedded miR944. Co-expression of immune checkpoint, T-regulatory, and Myeloid suppressor cells signatures may explain reduced efficacy of immune therapy. These findings support possibilities for molecular classification and therapeutic approaches.

Interest & Impact

Downloads

123 since deposited on 01 Oct 2019
15 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item