Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

Andrew M Gross; Ryan K Orosco; John P Shen; Ann Marie Egloff; Hannah Carter; Matan Hofree; Michel Choueiri; Charles S Coffey; Scott M Lippman; D Neil Hayes; Ezra E Cohen; Jennifer R Grandis; Quyen T Nguyen; Trey Ideker

doi:10.1038/ng.3051

Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

Nat Genet. 2014 Sep;46(9):939-43. doi: 10.1038/ng.3051. Epub 2014 Aug 3.

Authors

Affiliations

¹ Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, California, USA.
² Division of Head and Neck Surgery, University of California, San Diego, La Jolla, California, USA.
³ Department of Medicine, University of California, San Diego, La Jolla, California, USA.
⁴ Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁵ Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California, USA.
⁶ 1] Division of Head and Neck Surgery, University of California, San Diego, La Jolla, California, USA. [2] Department of Medicine, University of California, San Diego, La Jolla, California, USA. [3] Moores Cancer Center, University of California, San Diego, La Jolla, California, USA.
⁷ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁸ 1] Department of Medicine, University of California, San Diego, La Jolla, California, USA. [2] Moores Cancer Center, University of California, San Diego, La Jolla, California, USA.
⁹ 1] Division of Head and Neck Surgery, University of California, San Diego, La Jolla, California, USA. [2] Moores Cancer Center, University of California, San Diego, La Jolla, California, USA.
¹⁰ 1] Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, California, USA. [2] Department of Medicine, University of California, San Diego, La Jolla, California, USA. [3] Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California, USA. [4] Moores Cancer Center, University of California, San Diego, La Jolla, California, USA.

PMID: 25086664
PMCID: PMC4146706
DOI: 10.1038/ng.3051

Abstract

Head and neck squamous cell carcinoma (HNSCC) is characterized by aggressive behavior with a propensity for metastasis and recurrence. Here we report a comprehensive analysis of the molecular and clinical features of HNSCC that govern patient survival. We find that TP53 mutation is frequently accompanied by loss of chromosome 3p and that the combination of these events is associated with a surprising decrease in survival time (1.9 years versus >5 years for TP53 mutation alone). The TP53-3p interaction is specific to chromosome 3p and validates in HNSCC and pan-cancer cohorts. In human papillomavirus (HPV)-positive tumors, in which HPV inactivates TP53, 3p deletion is also common and is associated with poor outcomes. The TP53-3p event is modified by mir-548k expression, which decreases survival further, and is mutually exclusive with mutations affecting RAS signaling. Together, the identified markers underscore the molecular heterogeneity of HNSCC and enable a new multi-tiered classification of this disease.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / pathology
Child
Child, Preschool
Chromosome Deletion*
Chromosomes, Human, Pair 3
Genes, p53*
Genomics / methods
Head and Neck Neoplasms / genetics*
Head and Neck Neoplasms / pathology
Humans
Infant
Infant, Newborn
Middle Aged
Mutation
Prognosis
Squamous Cell Carcinoma of Head and Neck
Tumor Suppressor Protein p53 / genetics*
Young Adult

Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

Authors

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Abstract

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