Early Detection Research Network

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

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.

Akbani R, Al-Ahmadie H, Anur P, Benz C, Bowlby R, Brennan K, Bullman S, Byers LA, Campbell JD, Chen J, Chen TW, Chen Z, Cheng H, Cherniack AD, Chiu HS, Coarfa C, Creighton CJ, Diao L, Donehower L, Drill E, Fan H, Flores ER, Gay CM, Gevaert O, Gunaratne P, Hayes DN, Hegde A, Hoadley KA, Kanchi RS, Laird PW, Lazar AJ, Liu Y, Ma W, Mungall KL, Ojesina AI, Pedamallu CS, Peto M, Pickering CR, Prunello M, Rader JS, Robertson AG, Rustgi AK, Sadeghi S, Schultz A, Shen H, Shen R, Shih J, Stuart JM, Sumazin P, Taylor AM, Tsai KY, Van Waes C, Walter V, Wang C, Wang J, Weinstein JN, Wong CK, Yau C, Zhou JH, Zuna R

29617660

Cell Rep, 2018, 23 (1)

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