Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas.
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas.
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DOI：
10.1016/j.celrep.2018.03.063
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发表时间：
2018-04-03
期刊：
影响因子：
8.8
通讯作者：
Van Waes C
中科院分区：
文献类型：
--
作者：
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 HS;Chen TW;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
这项综合的多平台 PanCancer Atlas 研究从与吸烟和/或人乳头瘤病毒 (HPV) 相关的五个部位共同绘制并鉴定了鳞状细胞癌 (SCC) 的独特分子特征。 SCC 存在 3q、5p 和其他反复出现的染色体拷贝数改变 (CNA)、DNA 突变和/或基因和 microRNA 的异常甲基化，这些变异与鳞状细胞干性、上皮间质分化、生长、基因组完整性、氧化损伤、死亡和炎症相关的多基因程序的表达相关。低 CNA 的 SCC 往往是 HPV（+），并表现出高甲基化，并抑制 TET1 去甲基酶和 FANCF（之前与 SCC 易感性有关），或含有影响 CASP8、RAS-MAPK 通路、染色质修饰剂和免疫调节分子的突变。我们发现了驱动 ΔNp63 癌基因和嵌入 miR944 表达的替代启动子的低甲基化。免疫检查点、T 调节细胞和骨髓抑制细胞特征的共表达可能解释了免疫治疗疗效降低的原因。这些发现支持分子分类和治疗方法的可能性。简述坎贝尔等人。揭示来自不同组织部位的鳞状细胞癌可能与其他癌症区分开来，并通过染色体、DNA甲基化、信使和微小RNA表达的反复改变或突变进行分子亚分类。这些会影响鳞状细胞途径和为治疗提供候选的程序。
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. In Brief Campbell et al. reveal that squamous cell cancers from different tissue sites may be distinguished from other cancers and subclassified molecularly by recurrent alterations in chromosomes, DNA methylation, messenger and microRNA expression, or by mutations. These affect squamous cell pathways and programs that provide candidates for therapy.
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影响因子：
11.2
作者：
Eytan DF;Snow GE;Carlson S;Derakhshan A;Saleh A;Schiltz S;Cheng H;Mohan S;Cornelius S;Coupar J;Sowers AL;Hernandez L;Mitchell JB;Annunziata CM;Chen Z;Van Waes C
通讯作者：
Van Waes C
影响因子：
8
作者：
Ehsanian, R.;Brown, M.;Lu, H.;Yang, X. P.;Pattatheyil, A.;Yan, B.;Duggal, P.;Chuang, R.;Doondeea, J.;Feller, S.;Sudol, M.;Chen, Z.;Van Waes, C.
通讯作者：
Van Waes, C.
影响因子：
3.8
作者：
Gonzalez-Angulo AM;Hennessy BT;Meric-Bernstam F;Sahin A;Liu W;Ju Z;Carey MS;Myhre S;Speers C;Deng L;Broaddus R;Lluch A;Aparicio S;Brown P;Pusztai L;Symmans WF;Alsner J;Overgaard J;Borresen-Dale AL;Hortobagyi GN;Coombes KR;Mills GB
通讯作者：
Mills GB
影响因子：
5
作者：
Friedman, Jay A.;Wise, Stephanie C.;Van Waes, Carter
通讯作者：
Van Waes, Carter
影响因子：
1.9
作者：
Doecke, James D.;Wang, Ying;Baggerly, Keith
通讯作者：
Baggerly, Keith