%0 Journal Article %J Cell Rep %D 2018 %T Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas. %A Campbell, Joshua D %A Yau, Christina %A Bowlby, Reanne %A Liu, Yuexin %A Brennan, Kevin %A Fan, Huihui %A Taylor, Alison M %A Wang, Chen %A Walter, Vonn %A Akbani, Rehan %A Byers, Lauren Averett %A Creighton, Chad J %A Coarfa, Cristian %A Shih, Juliann %A Cherniack, Andrew D %A Gevaert, Olivier %A Prunello, Marcos %A Shen, Hui %A Anur, Pavana %A Chen, Jianhong %A Cheng, Hui %A Hayes, D Neil %A Bullman, Susan %A Pedamallu, Chandra Sekhar %A Ojesina, Akinyemi I %A Sadeghi, Sara %A Mungall, Karen L %A Robertson, A Gordon %A Benz, Christopher %A Schultz, Andre %A Kanchi, Rupa S %A Gay, Carl M %A Hegde, Apurva %A Diao, Lixia %A Wang, Jing %A Ma, Wencai %A Sumazin, Pavel %A Chiu, Hua-Sheng %A Chen, Ting-Wen %A Gunaratne, Preethi %A Donehower, Larry %A Rader, Janet S %A Zuna, Rosemary %A Al-Ahmadie, Hikmat %A Lazar, Alexander J %A Flores, Elsa R %A Tsai, Kenneth Y %A Zhou, Jane H %A Rustgi, Anil K %A Drill, Esther %A Shen, Ronglei %A Wong, Christopher K %A Stuart, Joshua M %A Laird, Peter W %A Hoadley, Katherine A %A Weinstein, John N %A Peto, Myron %A Pickering, Curtis R %A Chen, Zhong %A Van Waes, Carter %K Carcinoma, Squamous Cell %K Cell Line, Tumor %K DNA Methylation %K Epithelial-Mesenchymal Transition %K Gene Expression Regulation, Neoplastic %K Genomics %K Humans %K Metabolic Networks and Pathways %K Polymorphism, Genetic %X
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.
%B Cell Rep %V 23 %P 194-212.e6 %8 2018 Apr 03 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/29617660?dopt=Abstract %R 10.1016/j.celrep.2018.03.063