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Epigenetic modulation of signal transduction pathways in HPV-associated HNSCC.
- Source :
-
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery [Otolaryngol Head Neck Surg] 2013 Sep; Vol. 149 (3), pp. 409-16. Date of Electronic Publication: 2013 Jun 04. - Publication Year :
- 2013
-
Abstract
- Objective: Human papilloma virus (HPV) positive and HPV negative head and neck squamous cell cancer (HNSCC) are biologically distinct with a prognostic advantage for HPV positive patients compared to HPV negative cases. DNA promoter methylation is central to human diseases such as cancer, including HNSCC, with reported genome-wide hypomethylaton and promoter hypermethylation in HPV positive HNSCC tumors. The goal of this study was to identify differentially methylated genes in HPV positive versus HPV negative primary HNSCC genomes with clues to signaling networks.<br />Study Design: Laboratory-based study.<br />Setting: Primary care academic health care system.<br />Subjects and Methods: DNA from 4 HPV positive and 4 HPV negative freshly frozen primary HNSCC were subject to comprehensive genome-wide methylation profiling. Differentially methylated gene lists were examined using the Signal Transduction Pathways (canonical) filter in the Genomatix Pathway System (GePS).<br />Results: Twofold methylation differences were observed between HPV positive and HPV negative cases for 1168 genes. Pathway analysis applied to investigate the biological role of the 1168 differentially methylated genes revealed 8 signal transduction pathways forming a network of 66 genes, of which 62% are hypermethylated.<br />Conclusion: Our study reveals a predominant hypermethylation profile for genes in signal transduction pathways of HPV positive HNSCC tumor genomes. Because signaling events in the cell play a critical role in the execution of key biological functions, insights into how complex cellular signaling cascades and networks may be programmed in HNSCC are likely to be critical in the development of new biological agents designed to hit multiple targets.
- Subjects :
- Adult
Aged
Caveolin 1 genetics
DNA Methylation
ErbB Receptors genetics
Female
Gene Expression Profiling
Heparan Sulfate Proteoglycans genetics
Humans
Hyaluronan Receptors genetics
Male
Middle Aged
PPAR alpha genetics
PPAR gamma genetics
Pilot Projects
Receptor, ErbB-2 genetics
Syndecan-2 genetics
Carcinoma, Squamous Cell virology
Epigenomics
Head and Neck Neoplasms virology
Papillomaviridae genetics
Signal Transduction genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6817
- Volume :
- 149
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
- Publication Type :
- Academic Journal
- Accession number :
- 23736812
- Full Text :
- https://doi.org/10.1177/0194599813490895