Genomic and Transcriptomic Characterization Links Cell Lines with Aggressive Head and Neck Cancers

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.

Graphical Abstract

In Brief

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.