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

Campbell JD, Yau C, Bowlby R, Liu Y, Brennan K, Fan H, Taylor AM, Wang C, Walter V, Akbani R, Byers LA, Creighton CJ, Coarfa C, Shih J, Cherniack AD, Gevaert O, Prunello M, Shen H, Anur P, Chen J, Cheng H, Hayes DN, Bullman S, Pedamallu CS, Ojesina AI, Sadeghi S, Mungall KL, Robertson AG, Benz C, Schultz A, Kanchi RS, Gay CM, Hegde A, Diao L, Wang J, Ma W, Sumazin P, Chiu HS, Chen TW, 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 (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 23

Pages Range: 194-212.e6

Journal Issue: 1

DOI: 10.1016/j.celrep.2018.03.063

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.

Involved external institutions

Dana–Farber Cancer Institute United States (USA) (US) Buck Institute for Research on Aging United States (USA) (US) British Columbia Cancer Agency Canada (CA) University of Texas MD Anderson Cancer Center United States (USA) (US) Stanford University United States (USA) (US) Van Andel Institute United States (USA) (US) Mayo Clinic United States (USA) (US) University of Pennsylvania Health System (UPHS, Penn Medicine) United States (USA) (US) Houston Texas Medical Center United States (USA) (US) University of Houston United States (USA) (US) Medical College of Wisconsin (MCW) United States (USA) (US) University of Oklahoma United States (USA) (US) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) Roswell Park Cancer Institute United States (USA) (US) University of Pennsylvania United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) University of California Santa Cruz United States (USA) (US) University of North Carolina at Chapel Hill United States (USA) (US) Oregon Health and Science University (OSHU) United States (USA) (US) US National Institutes of Health (NIH) United States (USA) (US) University of Alabama at Birmingham (UAB) United States (USA) (US)

How to cite

APA:

Campbell, J.D., Yau, C., Bowlby, R., Liu, Y., Brennan, K., Fan, H.,... Van Waes, C. (2018). Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas. Cell Reports, 23(1), 194-212.e6. https://doi.org/10.1016/j.celrep.2018.03.063

MLA:

Campbell, Joshua D., et al. "Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas." Cell Reports 23.1 (2018): 194-212.e6.

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