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Identification of cryptic microaberrations in osteosarcoma by high-definition oligonucleotide array comparative genomic hybridization.
Selvarajah, Shamini; Yoshimoto, Maisa; Maire, Georges; Paderova, Jana; Bayani, Jane; Squire, Jeremy A; Zielenska, Maria.
Afiliação
  • Selvarajah S; Department of Pathology and Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Room 3-206, Toronto, Ontario M5G 1X8, Canada.
Cancer Genet Cytogenet ; 179(1): 52-61, 2007 Nov.
Article em En | MEDLINE | ID: mdl-17981215
Osteosarcoma (OS) is an aggressive bone tumor characterized by complex abnormal karyotypes and a high level of genomic instability. Using high-resolution array comparative genomic hybridization (aCGH), a novel class of localized copy number variations called microaberrations has been detected. These genomic anomalies typically involve DNA imbalances affecting 700 kb to 1 Mb DNA, and are often associated with some type of genetic syndromes. Because the origin of instability in OS is poorly understood, we used aCGH to determine whether microaberrations were a characteristic of four OS cell lines: U-2 OS, HOS, MG-63, and SAOS-2. TP53 is mutated in SAOS-2, a line in which 17 microaberrations were found. In contrast, U-2 OS, which has a wild-type TP53, had only six such anomalies, the lowest incidence. A 500-kb microaberration within a region of gain at 5p15.33 in SAOS-2 was confirmed by fluorescence in situ hybridization. Significantly, this genomic location is close to the TERT gene, a region of gain in all four cell lines. To our knowledge, this is the first systematic analysis of the incidence of microaberrations in OS. The high levels of these anomalies detected suggest that the instability processes in OS that lead to a highly abnormal karyotypes may also be associated with acquisition of genomic microaberrations.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ósseas / Osteossarcoma / Aberrações Cromossômicas / Análise de Sequência com Séries de Oligonucleotídeos Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2007 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ósseas / Osteossarcoma / Aberrações Cromossômicas / Análise de Sequência com Séries de Oligonucleotídeos Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2007 Tipo de documento: Article