| Abstract: |
Genetic gains and losses resulting from DNA strand breakage by ionizing radiation have been demonstrated in vitro and suspected in radiation-associated thyroid cancer. We hypothesized that copy number deviations might be more prevalent, and/or occur in genomic patterns, in tumors associated with presumptive DNA strand breakage from radiation exposure than in their spontaneous counterparts. We used cDNA microarray-based comparative genome hybridization to obtain genome-wide, high-resolution copy number profiles at 14,573 genomic loci in 23 post-Chernobyl and 20 spontaneous thyroid cancers. The prevalence of DNA gains in tumors from cases in exposed individuals was two- to fourfold higher than for cases in unexposed individuals and up to 10-fold higher for the subset of recurrent gains. DNA losses for all cases were low and more prevalent in spontaneous cases. We identified unique patterns of copy variation (mostly gains) that depended on a history of radiation exposure. Exposed cases, especially the young, harbored more recurrent gains that covered more of the genome. The largest regions, spanning 1.2 to 4.9 Mbp, were located at 1p36.32-.33, 2p23.2-.3, 3p21.1-.31, 6p22.1-.2, 7q36.1, 8q24.3, 9q34.11, 9q34.3, 11p15.5, 11q13.2-12.3, 14q32.33, 16p13.3, 16p11.2, 16q21-q12.2, 17q25.1, 19p13.31-qter, 22q11.21 and 22q13.2. Copy number changes, particularly gains, in post-Chernobyl thyroid cancer are influenced by radiation exposure and age at exposure, in addition to the neoplastic process. © 2006 by Radiation Research Society. |
| Keywords: |
adolescent; adult; child; clinical article; human tissue; child, preschool; mutation; in situ hybridization, fluorescence; prevalence; radiation injury; radiation exposure; age; dna strand breakage; dna; infant; sequence alignment; microarray analysis; oligonucleotide array sequence analysis; neoplasms, radiation-induced; nucleotide sequence; dna, neoplasm; genome; thyroid cancer; thyroid neoplasms; dna microarray; dna mutational analysis; gene dosage; comparative genomic hybridization; dna determination; chromosome 3p; chromosome 11q; chromosome 16q; gene location; complementary dna; chromosome 17q; chromosome 14q; chromosome 1p; chromosome 7q; chromosome 8q; chromosome mapping; sequence analysis, dna; chromosome 22q; chromosome 9q; chromosome 19p; chromosome 16p; chromosome 11p; chernobyl accident; ukraine; chromosome 2p; chromosome 6p; chernobyl nuclear accident; accidents, radiation; power plants
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