|Title||Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Campbell, 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|
|Date Published||2018 Apr 03|
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.
|Alternate Journal||Cell Rep|
|Grant List||P01 CA098101 / CA / NCI NIH HHS / United States|