Gene discovery in oral squamous cell carcinoma through the Head and Neck Cancer Genome Anatomy Project: confirmation by microarray analysis

Leethanakul, C; Knezevic, V; Patel, V; Amornphimoltham, P; Gillespie, J; Shillitoe, E.J; Emko, P; Park, M.H; Emmert-Buck, M.R; Strausberg, R.L; Krizman, D.B; Gutkind, J.S

doi:10.1016/S1368-8375(02)00107-0

« Previous Next »Oral Oncology
Volume 39, Issue 3 , Pages 248-258, April 2003

Gene discovery in oral squamous cell carcinoma through the Head and Neck Cancer Genome Anatomy Project: confirmation by microarray analysis

C Leethanakul
- Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, 30 Convent Drive, Building 30, Room 212, Bethesda, MD 20892-4340, USA
- Present address: Faculty of Dentistry, Prince of Songkla University, Hadd Yai, Songkhla 90112, Thailand.
V Knezevic
- Cancer Genome Anatomy Project, Office of the Director, National Cancer Institute, National Institutes of Health, Advanced Technology Center, 8717 Grovemont Circle, 134F, Gaithersburg, MD 20877, USA
- Present address: 20/20 GeneSystems, Inc., 9700 Great Seneca Highway, Rockville, MD 20850, USA.
V Patel
- Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, 30 Convent Drive, Building 30, Room 212, Bethesda, MD 20892-4340, USA
P Amornphimoltham
- Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, 30 Convent Drive, Building 30, Room 212, Bethesda, MD 20892-4340, USA
J Gillespie
- Science Applications International Corporation, National Cancer Institute, Bethesda, MD 20892, USA
E.J Shillitoe
- Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA
P Emko
- Department of Otolaryngology and Communication Sciences, SUNY Upstate Medical University, Syracuse, NY 13210, USA
M.H Park
- Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, 30 Convent Drive, Building 30, Room 212, Bethesda, MD 20892-4340, USA
M.R Emmert-Buck
- Pathogenetics Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
R.L Strausberg
- Cancer Genome Office, Building 3 Room 11A03, Bethesda, MD 20892, USA
D.B Krizman
- Pathogenetics Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
J.S Gutkind
- Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, 30 Convent Drive, Building 30, Room 212, Bethesda, MD 20892-4340, USA
- Corresponding author. Tel.: +1-301-496-6259; fax +1-301-402-0823

Abstract

The near completion of the human genome project and the recent development of novel, highly sensitive high-throughput techniques have now afforded the unique opportunity to perform a comprehensive molecular characterization of normal, precancerous, and malignant cells, including those derived from squamous carcinomas of the head and neck (HNSCC). As part of these efforts, representative cDNA libraries from patient sets, comprising of normal and malignant squamous epithelium, were generated and contributed to the Head and Neck Cancer Genome Anatomy Project (HN-CGAP). Initial analysis of the sequence information indicated the existence of many novel genes in these libraries [Oral Oncol 36 (2000) 474]. In this study, we surveyed the available sequence information using bioinformatic tools and identified a number of known genes that were differentially expressed in normal and malignant epithelium. Furthermore, this effort resulted in the identification of 168 novel genes. Comparison of these clones to the human genome identified clusters in loci that were not previously recognized as being altered in HNSCC. To begin addressing which of these novel genes are frequently expressed in HNSCC, their DNA was used to construct an oral-cancer-specific microarray, which was used to hybridize α-³³P dCTP labeled cDNA derived from five HNSCC patient sets. Initial assessment demonstrated 10 clones to be highly expressed (>2-fold) in the normal squamous epithelium, while 14 were highly represented in the malignant counterpart, in three of the five patient sets, thus suggesting that a subset of these newly discovered transcripts might be highly expressed in this tumor type. These efforts, together with other multi-institutional genomic and proteomic initiatives are expected to contribute to the complete understanding of the molecular pathogenesis of HNSCCs, thus helping to identify new markers for the early detection of preneoplastic lesions and novel targets for pharmacological intervention in this disease.

Keywords: Oral epithelium, Oral cancer, LCM, Gene expression, cDNA microarrays, CGAP