Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
Translational Bioinformatics, MedImmune, Gaithersburg, MD 20878, USA.
Cell Rep. 2018 Oct 30;25(5):1332-1345.e5. doi: 10.1016/j.celrep.2018.10.007.
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.
细胞系是生物学和临床前研究的重要工具，建立它们与肿瘤中基因组改变的关系可以加速功能和治疗发现。我们对 15 个人乳头瘤病毒（HPV）阴性和 11 个人乳头瘤病毒阳性头颈部鳞状细胞癌（HNSCC）细胞系的基因组和转录组谱进行了综合分析，并与癌症基因组图谱（TCGA）中的 279 个肿瘤进行了比较。我们在染色体 3q22-29、5p15、11q13/22 和 8p11 上发现了反复扩增，这些扩增驱动了超过 100 个基因在细胞系和肿瘤中的高表达。这些改变，加上肿瘤抑制基因的缺失或突变，集中在重要的信号通路，重现了侵袭性 HNSCC 的基因组景观。在这些改变中，大多数 HPV(-)细胞系中同时存在 3q26.3 扩增和 TP53 突变，反映了预后较差的肿瘤。我们的研究结果阐明和验证了 HNSCC 细胞系中许多发现所依赖的基因组改变，并为未来的研究提供了有价值的模型。
