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

Cell Rep. 2018 Oct 30;25(5):1332-1345.e5. doi: 10.1016/j.celrep.2018.10.007.

Abstract

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

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Cell Line, Tumor
  • Chromosomes, Human / genetics
  • DNA Copy Number Variations / genetics
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic
  • Genome*
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / virology
  • Humans
  • Mutation / genetics
  • Neoplasm Invasiveness
  • Papillomaviridae / pathogenicity
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / genetics
  • Transcriptome / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • RNA, Messenger
  • Tumor Suppressor Protein p53