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
KeywordsCarcinoma, Squamous Cell, Cell Line, Tumor, DNA Methylation, Epithelial-Mesenchymal Transition, Gene Expression Regulation, Neoplastic, Genomics, Humans, Metabolic Networks and Pathways, Polymorphism, Genetic
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
PubMed Central IDPMC6002769
Grant ListU24 CA143882 / CA / NCI NIH HHS / United States
U24 CA143866 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
P30 CA225520 / CA / NCI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
P01 CA098101 / CA / NCI NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
ZID DC000075-09 / ImNIH / Intramural NIH HHS / United States
U24 CA210949 / CA / NCI NIH HHS / United States
R01 CA163722 / CA / NCI NIH HHS / United States
U24 CA210990 / CA / NCI NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
ZIA DC000016-24 / ImNIH / Intramural NIH HHS / United States
ZIA DC000074-09 / ImNIH / Intramural NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
U24 CA210950 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
R01 CA194062 / CA / NCI NIH HHS / United States
U24 CA210957 / CA / NCI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
U24 CA210969 / CA / NCI NIH HHS / United States
U24 CA210988 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U24 CA199461 / CA / NCI NIH HHS / United States
R35 CA197452 / CA / NCI NIH HHS / United States
T32 CA009666 / CA / NCI NIH HHS / United States

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