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.

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

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53

Supplementary concepts

  • Chromosome 3, monosomy 3p