Journal Article

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

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

2014

Overview

Trey Ideker and colleagues report a comprehensive genome-wide analysis of head and neck squamous cell carcinoma, reporting that TP53 mutations are frequently accompanied by loss of chromosome 3p. Their data indicate that the combination of these two events has a stronger negative effect on survival rate than either event alone. 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 45/23 / 49/39 / 692/308/1892 / 692/308/2056 / 692/308/409 / 692/699/67/1536 / Adolescent / Adult / Aged / Aged, 80 and over / Aggressive behavior / Agriculture / Analysis / Animal Genetics and Genomics / Basketball players / Biomedicine / Cancer / Cancer genetics / Cancer metastasis / Cancer Research / Carcinoma / Carcinoma, Squamous Cell - genetics / Carcinoma, Squamous Cell - pathology / Child / Child, Preschool / Chromosome Deletion / Chromosomes / Chromosomes, Human, Pair 3 / Clinical outcomes / Data processing / Development and progression / Diseases / Gene expression / Gene Function / Genes, p53 / Genetic aspects / Genetic research / Genomes / Genomics / Genomics - methods / Head and neck cancer / Head and Neck Neoplasms - genetics / Head and Neck Neoplasms - pathology / Heterogeneity / Human Genetics / Humans / Infant / Infant, Newborn / Medical prognosis / Medical research / Middle Aged / Mutation / Papillomavirus / Papillomavirus infections / Prognosis / Properties / Squamous cell carcinoma / Squamous Cell Carcinoma of Head and Neck / Studies / Survival analysis / Time / Tumor proteins / Tumor Suppressor Protein p53 - genetics / Tumors / Young Adult