Presented at the Meeting of the Eastern Section of the American Laryngological, Rhinological and Otological Society, Inc., Pittsburgh, Pennsylvania, January 30, 2000.
Genome-Wide Screening for Radiation Response Factors in Head and Neck Cancer†
Article first published online: 2 JAN 2009
Copyright © 2000 The Triological Society
Volume 110, Issue 8, pages 1251–1256, August 2000
How to Cite
Singh, B., Kim, S.-H., Carew, J. F., Yu, I., Shaha, A. R., Wolden, S., Boyle, J., Shah, J. P. and Rao, P. H. (2000), Genome-Wide Screening for Radiation Response Factors in Head and Neck Cancer. The Laryngoscope, 110: 1251–1256. doi: 10.1097/00005537-200008000-00005
Supported in part by grants TA32 CA 09685 (b.s.) from the United States Public Health Service and the Young Investigator Award (b.s.) from the American Society of Clinical Oncology.
- Issue published online: 2 JAN 2009
- Article first published online: 2 JAN 2009
- Manuscript Accepted: 27 APR 2000
- Radiation therapy;
- comparative genomic hybridization;
- squamous cell carcinoma;
- head and neck neoplasms;
- cell lines.
Introduction Radiation therapy is an integral part of the treatment of head and neck cancer. Factors predicting radiation response are ill defined. The aim of this study was to identify genetic aberrations associated with radiation response in cell lines derived from head and neck squamous cell carcinomas (HNSCC) using comparative genomic hybridization (CGH) for genome-wide screening.
Methods Five cell lines derived from HNSCC were subjected to a single course of radiation (400 cGy) in parallel with a similarly handled, untreated control. Cellular response to radiation was determined on posttreatment days 1, 2, 3, 4, and 5 using a cell viability assay (MTT assay). Radiation response was defined as 35% or greater decrease in cell survival relative to control. Tumor doubling time was determined by cell counts performed at day 0 and 1 for each cell line. All experiments were done in quadruplicate. CGH analysis was performed by differentially labeling DNA from tumor and normal tissue with fluorescent agents. The labeled DNAs were simultaneously hybridized to normal metaphase chromosomes. Image analysis for fluorescence intensity along the entire length of each metaphase chromosome allowed generation of a color ratio, which was used to detect copy number changes.
Results Radioresistance was identified in two of five cell lines. The tumor doubling time was not a predictor of radiation response. CGH identified a complex pattern of aberrations, with gain of 3q common to all cell lines. The number of genetic aberration was higher in radiation-sensitive cell lines than in radiation-resistant ones. No recurrent aberrations were unique to the radiation-resistant cell lines. Recurrent gains at 7p and 17q and losses at 5q, 7q, and 18q were unique to the radiation-sensitive cell lines.
Conclusions The number of aberrations identified by CGH analysis may be a predictor of radiation response. A large study of primary tumors is warranted to confirm this association and identify specific genetic aberrations associated with radiation response.