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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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, 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; Cancer Genome Atlas Research Network, ; Stuart, JM; Laird, PW; Hoadley, KA; Weinstein, JN; Peto, M; Pickering, CR; Chen, Z; Van Waes, C

Published Date

  • April 3, 2018

Published In

Volume / Issue

  • 23 / 1

Start / End Page

  • 194 - 212.e6

PubMed ID

  • 29617660

Pubmed Central ID

  • 29617660

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2018.03.063

Language

  • eng

Conference Location

  • United States