Genomic and Transcriptomic Characterization Links Cell Lines with Aggressive Head and Neck Cancers.
Genomic and Transcriptomic Characterization Links Cell Lines with Aggressive Head and Neck Cancers.
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DOI：
10.1016/j.celrep.2018.10.007
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发表时间：
2018-10-30
期刊：
影响因子：
8.8
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Cheng H;Yang X;Si H;Saleh AD;Xiao W;Coupar J;Gollin SM;Ferris RL;Issaeva N;Yarbrough WG;Prince ME;Carey TE;Van Waes C;Chen Z
细胞系是生物学和临床前研究的重要工具，建立它们与肿瘤基因组改变的关系可以加速功能和治疗的发现。我们对 15 个人乳头瘤病毒 (HPV) 阴性和 11 个 HPV 阳性头颈鳞状细胞癌 (HNSCC) 系的基因组和转录组图谱进行了综合分析，以与癌症基因组图谱 (TCGA) 中的 279 个肿瘤进行比较。我们发现染色体 3q22-29、5p15、11q13/22 和 8p11 上的反复扩增可驱动细胞系和肿瘤中 100 多个基因的表达增加。这些改变，加上肿瘤抑制基因的丢失或突变，集中在重要的信号传导通路上，重现了侵袭性 HNSCC 的基因组景观。其中，大多数 HPV(-) 细胞系中同时存在 3q26.3 扩增和 TP53 突变，反映出肿瘤的存活率较差。我们的研究结果阐明并验证了基因组改变，这些改变支撑了 HNSCC 系的众多发现，并为未来的研究提供了有价值的模型。程等人。揭示头颈鳞状细胞癌细胞系表现出在预后较差的肿瘤中发现的反复染色体拷贝数改变和突变。拷贝改变与鳞状细胞信号通路和程序中涉及的多个基因的表达相关，这些基因为机制研究和靶向治疗提供了候选者。
Cell lines are important tools for biological and preclinical investigation, and establishing their relationship to genomic alterations in tumors could accelerate functional and therapeutic discoveries. We conducted integrated analyses of genomic and transcriptomic profiles of 15 human papillomavirus (HPV)-negative and 11 HPV-positive head and neck squamous cell carcinoma (HNSCC) lines to compare with 279 tumors from The Cancer Genome Atlas (TCGA). We identified recurrent amplifications on chromosomes 3q22–29, 5p15, 11q13/22, and 8p11 that drive increased expression of more than 100 genes in cell lines and tumors. These alterations, together with loss or mutations of tumor suppressor genes, converge on important signaling pathways, recapitulating the genomic landscape of aggressive HNSCCs. Among these, concurrent 3q26.3 amplification and TP53 mutation in most HPV(–) cell lines reflect tumors with worse survival. Our findings elucidate and validate genomic alterations underpinning numerous discoveries made with HNSCC lines and provide valuable models for future studies. Cheng et al. reveal that head and neck squamous cell cancer cell lines display recurrent chromosome copy number alterations and mutations found in tumors with worse prognosis. The copy alterations correlate with expression of multiple genes implicated in squamous cell signaling pathways and programs that provide candidates for mechanistic studies and targeted 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：
7.3
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Schultz N
影响因子：
5.8
作者：
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通讯作者：
Schlesner, Matthias
影响因子：
16.6
作者：
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通讯作者：
D'Silva, Nisha J.
影响因子：
9.8
作者：
Fromer, Menachem;Moran, Jennifer L.;Purcell, Shaun M.
通讯作者：
Purcell, Shaun M.