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

TitleGenomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas.
Publication TypeJournal Article
Year of Publication2018
AuthorsCampbell, JD, Yau, C, Bowlby, R, Liu, Y, Brennan, K, Fan, H, Taylor, AM, Wang, C, Walter, V, Akbani, R, Byers, LAverett, Creighton, CJ, Coarfa, C, Shih, J, Cherniack, AD, Gevaert, O, Prunello, M, Shen, H, Anur, P, Chen, J, Cheng, H, D Hayes, N, Bullman, S, Pedamallu, CSekhar, Ojesina, AI, Sadeghi, S, Mungall, KL, A Robertson, G, Benz, C, Schultz, A, Kanchi, RS, Gay, CM, Hegde, A, Diao, L, Wang, J, Ma, W, Sumazin, P, Chiu, H-S, Chen, T-W, Gunaratne, P, Donehower, L, Rader, JS, Zuna, R, Al-Ahmadie, H, Lazar, AJ, Flores, ER, Tsai, KY, Zhou, JH, Rustgi, AK, Drill, E, Shen, R, Wong, CK, Stuart, JM, Laird, PW, Hoadley, KA, Weinstein, JN, Peto, M, Pickering, CR, Chen, Z, Van Waes, C
Corporate AuthorsCancer Genome Atlas Research Network
JournalCell Rep
Volume23
Issue1
Pagination194-212.e6
Date Published2018 Apr 03
ISSN2211-1247
Abstract

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.

DOI10.1016/j.celrep.2018.03.063
Alternate JournalCell Rep
PubMed ID29617660