title: Cyclin E1 is amplified and overexpressed in osteosarcoma.
abstract: Osteosarcoma is a genetically complex malignancy, predominantly afflicting the adolescent population and associated still with relatively poor long-term outcomes. Although there has been some improvement in the understanding of osteosarcoma biology, this has not yet translated particularly well into therapeutic advances. By using a whole-genome tiling path array for comparative genomic hybridization analysis, we sought to evaluate DNA copy number changes in 22 osteosarcoma tumor samples. Regions of most frequent gains or losses generated by Genomic Identification of Significant Targets in Cancer analysis were evaluated for genes of interest. Correlation of the copy number data with preexisting expression data for these genes yielded not only targets known to be important in osteosarcoma but also novel targets, notably cyclin E1. Fluorescence in situ hybridization and immunohistochemical analysis confirmed the findings. Overexpression of cyclin E1 has potential prognostic and therapeutic implications that are discussed herein.
authors: British Columbia Cancer Research Center, Vancouver, British Columbia, Canada.
authors: William W
authors: WW
authors: Lockwood
authors: Deirdre
authors: D
authors: Stack
authors: Thomas
authors: T
authors: Morris
authors: David
authors: D
authors: Grehan
authors: Conor
authors: C
authors: O'Keane
authors: Greg L
authors: GL
authors: Stewart
authors: Joanna
authors: J
authors: Cumiskey
authors: Wan L
authors: WL
authors: Lam
authors: Jeremy A
authors: JA
authors: Squire
authors: David M
authors: DM
authors: Thomas
authors: Maureen J
authors: MJ
authors: O'Sullivan
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D019927:Cyclin E / Q000235:genetics*; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D015513:Oncogene Proteins / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins