genomic instability and telomere fusion of canine osteosarcoma cells基因组不稳定性和犬骨肉瘤细胞的端粒融合.pdfVIP

Genomic Instability and Telomere Fusion of Canine Osteosarcoma Cells 1 1 1 1 1 1 Junko Maeda , Charles R. Yurkon , Hiroshi Fujisawa , Masami Kaneko , Stefan C. Genet , Erica J. Roybal , 1 1 2 1 2 Garrett W. Rota , Ethan R. Saffer , Barbara J. Rose , William H. Hanneman , Douglas H. Thamm , Takamitsu A. Kato1* 1 Department of Environmental Radiological Health Sciences, Colorado State University, Fort Collins, Colorado, United States of America, 2 Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado, United States of America Abstract Canine osteosarcoma (OSA) is known to present with highly variable and chaotic karyotypes, including hypodiploidy, hyperdiploidy, and increased numbers of metacentric chromosomes. The spectrum of genomic instabilities in canine OSA has significantly augmented the difficulty in clearly defining the biological and clinical significance of the observed cytogenetic abnormalities. In this study, eight canine OSA cell lines were used to investigate telomere fusions by fluorescence in situ hybridization (FISH) using a peptide nucleotide acid probe. We characterized each cell line by classical cytogenetic studies and cellular phenotypes including telomere associated factors and then evaluated correlations from this data. All eight canine OSA cell lines displayed increased abnormal metacentric chromosomes and exhibited numerous telomere fusions and interstitial telomeric signals. Also, as evidence of unstable telomeres, colocalization of c-H2AX a