Cell Reports
Volume 25, Issue 5, 30 October 2018, Pages 1332-1345.e5
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Genomic and Transcriptomic Characterization Links Cell Lines with Aggressive Head and Neck Cancers

https://doi.org/10.1016/j.celrep.2018.10.007Get rights and content
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Highlights

  • Genomic and transcriptomic landscape of 26 HNSCC lines compared with 279 TCGA tumors

  • Copy gains of chromosomes 3q, 5p, and 11q drive increased oncogene expression

  • Concurrent 3q26.3 amplification and TP53 mutation are associated with worse survival

  • Cell lines recapitulate genomic alterations of more aggressive HNSCC tumor subtypes

Summary

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.

Keywords

head and neck squamous cell carcinoma
cell lines
The Cancer Genome Atlas
human papilloma virus
copy number
NFE2L2
PIK3CA
SOX2
TP63
FADD
BIRC2

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