Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas.
Abstact
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.
Authors
- 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