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

TitleMulti-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss.
Publication TypeJournal Article
Year of Publication2014
AuthorsGross AM, Orosco RK, Shen JP, Egloff AMarie, Carter H, Hofree M, Choueiri M, Coffey CS, Lippman SM, D Hayes N, Cohen EE, Grandis JR, Nguyen QT, Ideker T
JournalNat Genet
Volume46
Issue9
Pagination939-43
Date Published2014 Sep
ISSN1546-1718
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell, Child, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 3, Genes, p53, Genomics, Head and Neck Neoplasms, Humans, Infant, Infant, Newborn, Middle Aged, Mutation, Prognosis, Tumor Suppressor Protein p53, Young Adult
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.

DOI10.1038/ng.3051
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/25086664?dopt=Abstract
Alternate JournalNat. Genet.
PubMed ID25086664
PubMed Central IDPMC4146706
Grant ListDP5 OD017937 / OD / NIH HHS / United States
DP5 OD017937-01 / OD / NIH HHS / United States
K07 CA137140 / CA / NCI NIH HHS / United States
P30 CA023100 / CA / NCI NIH HHS / United States
P41 GM103504 / GM / NIGMS NIH HHS / United States
P41 GM103504 / GM / NIGMS NIH HHS / United States
P41 RR031228 / RR / NCRR NIH HHS / United States
P50 CA097190 / CA / NCI NIH HHS / United States
P50 GM085764 / GM / NIGMS NIH HHS / United States
P50 GM085764 / GM / NIGMS NIH HHS / United States
R01 CA158448 / CA / NCI NIH HHS / United States
R01 EB014929 / EB / NIBIB NIH HHS / United States
T32 DC000028 / DC / NIDCD NIH HHS / United States
T32 DC000028 / DC / NIDCD NIH HHS / United States
U24 CA184427 / CA / NCI NIH HHS / United States
U24 CA184427 / CA / NCI NIH HHS / United States
UL1 TR000005 / TR / NCATS NIH HHS / United States
Track(s): 
Bioinformatics and Systems Biology