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Genome‐Wide Screening for Radiation Response Factors in Head and Neck Cancer
Author(s) -
Singh Bhuvanesh,
Kim SeHeon,
Carew John F.,
Yu Irene,
Shaha Ashok R.,
Wolden Suzanne,
Boyle Jay,
Shah Jatin P.,
Rao Pulivarti H.
Publication year - 2000
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200008000-00005
Subject(s) - radioresistance , doubling time , metaphase , comparative genomic hybridization , biology , cell culture , head and neck cancer , radiation therapy , cancer , chromosome , cancer research , pathology , medicine , genetics , gene
Abstract 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.