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

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

Author information

1
Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
2
Translational Bioinformatics, MedImmune, Gaithersburg, MD 20878, USA.
3
Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
4
Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15260, USA.
5
Division of Head and Neck Surgery, Departments of Otolaryngology, Radiation Oncology, and Immunology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.
6
Department of Surgery, Division of Otolaryngology, Molecular Virology Research Program, Smilow Cancer Hospital, Yale Cancer Center, Yale University Medical School, New Haven, CT 06520, USA.
7
Cancer Biology Program, Program in the Biomedical Sciences, Rackham Graduate School, and the Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
8
Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA. Electronic address: vanwaesc@nidcd.nih.gov.
9
Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA. Electronic address: chenz@nidcd.nih.gov.

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

PMID:
30380422
DOI:
10.1016/j.celrep.2018.10.007
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