Genomic signatures of chromosomal instability and osteosarcoma progression detected by high resolution array CGH and interphase FISH
| العنوان: | Genomic signatures of chromosomal instability and osteosarcoma progression detected by high resolution array CGH and interphase FISH |
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| المؤلفون: | S. Selvarajah, Maisa Yoshimoto, Paul S. Thorner, Maria Zielenska, Olga Ludkovski, Paul C. Park, Jane Bayani, Georges Maire, Jeremy A. Squire |
| المصدر: | Cytogenetic and Genome Research. 122:5-15 |
| بيانات النشر: | S. Karger AG, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Male, musculoskeletal diseases, Chromosomes, Artificial, Bacterial, Adolescent, Gene Dosage, High resolution, Bone Neoplasms, Biology, Chromosomal Instability, Chromosome instability, Genetics, medicine, Humans, Child, Interphase, Molecular Biology, In Situ Hybridization, Fluorescence, Genetics (clinical), Oligonucleotide Array Sequence Analysis, Osteosarcoma, Karyotype, Prognosis, medicine.disease, Molecular biology, Karyotyping, Fish |
| الوصف: | Osteosarcoma (OS) is characterized by an unstable karyotype which typically has a heterogeneous pattern of complex chromosomal abnormalities. High-resolution array comparative genomic hybridization (CGH) in combination with interphase fluorescence in situ hybridization (FISH) analyses provides a complete description of genomic imbalances together with an evaluation of the contribution of cell-to-cell variation to copy number changes. There have been no analyses to date documenting genomic signatures consistent with chromosomal instability mechanisms in OS tumors using array CGH. In this study, we utilized high-resolution array CGH to identify and characterize recurrent signatures of genomic imbalances using ten OS tumors. Comparison between the genomic profiles identified tumor groups with low, intermediate and high levels of genomic imbalance. Bands 6p22→p21, 8q24 and 17p12→ p11.2 were consistently involved in high copy gain or amplification events. Since these three locations have been consistently associated with OS oncogenesis, FISH probes from each cytoband were used to derive an index of cellular heterogeneity for copy number within each region. OS with the highest degree of genomic imbalance also exhibited the most extreme cell-to-cell copy number variation. Significantly, the three OS with the most imbalance and genomic copy number heterogeneity also had the poorest response to preoperative chemotherapy. This genome wide analysis is the first utilizing oligonucleotide array CGH in combination with FISH analysis to derive genomic signatures of chromosomal instability in OS tumors by studying genomic imbalance and intercellular heterogeneity. This comprehensive genomic screening approach provides important insights concerning the mechanisms responsible for generating complex genomes. The resulting phenotypic diversity can generate tumors with a propensity for an aggressive disease course. A better understanding of the underlying mechanisms leading to OS tumor development could result in the identification of prognostic markers and therapeutic targets. |
| تدمد: | 1424-859X 1424-8581 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6f3c4578654ace184b72d1bbf5ce8f4Test https://doi.org/10.1159/000151310Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....d6f3c4578654ace184b72d1bbf5ce8f4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1424859X 14248581 |
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