Campbell, Joshua DJoshua DCampbellYau, ChristinaChristinaYauBowlby, ReanneReanneBowlbyLiu, YuexinYuexinLiuBrennan, KevinKevinBrennanFan, HuihuiHuihuiFanTaylor, Alison MAlison MTaylorWang, ChenChenWangWalter, VonnVonnWalterAkbani, RehanRehanAkbaniByers, Lauren AverettLauren AverettByersCreighton, Chad JChad JCreightonCoarfa, CristianCristianCoarfaShih, JuliannJuliannShihCherniack, Andrew DAndrew DCherniackGevaert, OlivierOlivierGevaertPrunello, MarcosMarcosPrunelloShen, HuiHuiShenAnur, PavanaPavanaAnurChen, JianhongJianhongChenCheng, HuiHuiChengHayes, D NeilD NeilHayesBullman, SusanSusanBullmanPedamallu, Chandra SekharChandra SekharPedamalluOjesina, Akinyemi IAkinyemi IOjesinaSadeghi, SaraSaraSadeghiMungall, Karen LKaren LMungallRobertson, A GordonA GordonRobertsonBenz, ChristopherChristopherBenzSchultz, AndreAndreSchultzKanchi, Rupa SRupa SKanchiGay, Carl MCarl MGayHegde, ApurvaApurvaHegdeDiao, LixiaLixiaDiaoWang, JingJingWangMa, WencaiWencaiMaSumazin, PavelPavelSumazinChiu, Hua-ShengHua-ShengChiuChen, Ting-WenTing-WenChenGunaratne, PreethiPreethiGunaratneDonehower, LarryLarryDonehowerRader, Janet SJanet SRaderZuna, RosemaryRosemaryZunaAl-Ahmadie, HikmatHikmatAl-AhmadieLazar, Alexander JAlexander JLazarFlores, Elsa RElsa RFloresTsai, Kenneth YKenneth YTsaiZhou, Jane HJane HZhouRustgi, Anil KAnil KRustgiDrill, EstherEstherDrillShen, RongleiRongleiShenWong, Christopher KChristopher KWong2024-10-082024-10-082018-04-03https://boris-portal.unibe.ch/handle/20.500.12422/64171This 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.enbladder carcinoma with squamous differentiation cervical squamous cell carcinoma esophageal squamous cell carcinoma genomics head and neck squamous cell carcinoma human papillomavirus lung squamous cell carcinoma proteomics transcriptomics600 - Technology::610 - Medicine & healtharticle10.7892/boris.1263872961766010.1016/j.celrep.2018.03.063