TY - JOUR
T1 - Oncogenic Properties of Candidate Oncogenes in Chromosome Region 17p11.2p12 in Human Osteosarcoma
AU - Both, Joeri
AU - Wu, Thijs
AU - ten Asbroek, Anneloor L. M. A.
AU - Baas, Frank
AU - Hulsebos, Theo J. M.
PY - 2016
Y1 - 2016
N2 - 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
AB - 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
U2 - https://doi.org/10.1159/000451046
DO - https://doi.org/10.1159/000451046
M3 - Article
C2 - 27846620
SN - 1424-8581
VL - 150
SP - 52
EP - 59
JO - Cytogenetic and genome research
JF - Cytogenetic and genome research
IS - 1
ER -