Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation
| Autor: | Markus Heidenblad, Karoly Szuhai, Pancras C.W. Hogendoorn, F Vult von Steyern, Fredrik Mertens, Marije IJszenga, Göran Jönsson, Johan Staaf, Nils Mandahl, Karolin H. Hallor, Henrik C. F. Bauer |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male musculoskeletal diseases Cancer Research Gene Dosage Locus (genetics) Biology Gene dosage Genome CDKN2A 03 medical and health sciences 0302 clinical medicine Chordoma medicine Humans array CGH Molecular Diagnostics Gene In Situ Hybridization Fluorescence Aged Cyclin-Dependent Kinase Inhibitor p15 Oligonucleotide Array Sequence Analysis 030304 developmental biology Aged 80 and over Chromosome Aberrations Genetics 0303 health sciences Spinal Neoplasms genomic imbalances Genes p16 Nucleic Acid Hybridization Karyotype Middle Aged medicine.disease Oncology 030220 oncology & carcinogenesis Female Chromosomes Human Pair 9 Gene Deletion Comparative genomic hybridization |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6604130 |
| Popis: | The initiating somatic genetic events in chordoma development have not yet been identified. Most cytogenetically investigated chordomas have displayed near-diploid or moderately hypodiploid karyotypes, with several numerical and structural rearrangements. However, no consistent structural chromosome aberration has been reported. This is the first array-based study characterising DNA copy number changes in chordoma. Array comparative genomic hybridisation (aCGH) identified copy number alterations in all samples and imbalances affecting 5 or more out of the 21 investigated tumours were seen on all chromosomes. In general, deletions were more common than gains and no high-level amplification was found, supporting previous findings of primarily losses of large chromosomal regions as an important mechanism in chordoma development. Although small imbalances were commonly found, the vast majority of these were detected in single cases; no small deletion affecting all tumours could be discerned. However, the CDKN2A and CDKN2B loci in 9p21 were homo- or heterozygously lost in 70% of the tumours, a finding corroborated by fluorescence in situ hybridisation, suggesting that inactivation of these genes constitute an important step in chordoma development. |
| Databáze: | OpenAIRE |
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