title: Oncogenic Properties of Candidate Oncogenes in Chromosome Region 17p11.2p12 in Human Osteosarcoma.
abstract: Osteosarcomas are primary tumors of bone that most often develop in adolescents. They are characterized by complex genomic changes including amplifications, deletions, and translocations. The chromosome region 17p11.2p12 is frequently amplified in human high grade osteosarcomas (25% of cases), suggesting the presence of one or more oncogenes. In previous studies, we identified 9 candidate oncogenes in this region (GID4, ARGHAP44, LRRC75A-AS1, TOP3A, COPS3, SHMT1, PRPSAP2, PMP22, and RASD1). The aim of the present study was to determine their oncogenic properties. Therefore, we generated osteosarcoma cell lines overexpressing these genes, except for LRRC75A-AS1 and PRPSAP2, and subjected these to functional oncogenic assays. We found that TOP3A, SHMT1, and RASD1 overexpression provided increased proliferation and that ARGHAP44, COPS3, and PMP22 overexpression had a stimulatory effect on migration and invasion of the cells. COPS3 and PMP22 overexpression additionally improved the ability of the cells to form new colonies. No oncogenic effect could be demonstrated for GID4 overexpression. We conclude that the concerted amplification-mediated overexpression of these genes in 17p11.2p12 may contribute to the oncogenic process in malignant osteosarcoma.
authors.affiliation: Department of Genome Analysis, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Joeri
authors.initials: J
authors.lastname: Both
authors.forename: Thijs
authors.initials: T
authors.lastname: Wu
authors.forename: Anneloor L M A
authors.initials: AL
authors.lastname: Ten Asbroek
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Hulsebos
mesh_terms: D000075686:COP9 Signalosome Complex; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D009857:Oncogenes / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C539906:ARHGAP44 protein, human; C477661:COPS3 protein, human; D020690:GTPase-Activating Proteins; D009185:Myelin Proteins; C073687:PMP22 protein, human; D011518:Proto-Oncogene Proteins; C400132:RASD1 protein, human; D012696:Glycine Hydroxymethyltransferase; C520541:SHMT protein, human; D000075686:COP9 Signalosome Complex; D018631:ras Proteins; D004264:DNA Topoisomerases, Type I