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
PubMed ID
Appears In
Cell Rep, 2018, 23 (1)