Format

Send to

Choose Destination
Cancer Discov. 2013 Jul;3(7):770-81. doi: 10.1158/2159-8290.CD-12-0537. Epub 2013 Apr 25.

Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers.

Author information

1
Departments of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.

Abstract

The survival of patients with oral squamous cell carcinoma (OSCC) has not changed significantly in several decades, leading clinicians and investigators to search for promising molecular targets. To this end, we conducted comprehensive genomic analysis of gene expression, copy number, methylation, and point mutations in OSCC. Integrated analysis revealed more somatic events than previously reported, identifying four major driver pathways (mitogenic signaling, Notch, cell cycle, and TP53) and two additional key genes (FAT1, CASP8). The Notch pathway was defective in 66% of patients, and in follow-up studies of mechanism, functional NOTCH1 signaling inhibited proliferation of OSCC cell lines. Frequent mutation of caspase-8 (CASP8) defines a new molecular subtype of OSCC with few copy number changes. Although genomic alterations are dominated by loss of tumor suppressor genes, 80% of patients harbored at least one genomic alteration in a targetable gene, suggesting that novel approaches to treatment may be possible for this debilitating subset of head and neck cancers.

PMID:
23619168
PMCID:
PMC3858325
DOI:
10.1158/2159-8290.CD-12-0537
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center