Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma

Xin Yan Lu, Yaojuan Lu, Yi Jue Zhao, Kim Jaeweon, Jason Kang, Xiao Nan Li, Gouqing Ge, Rene Meyer, Laszlo Perlaky, John Hicks, Murali Chintagumpala, Wei Wen Cai, Marc Ladanyi, Richard Gorlick, Ching C. Lau, Debananda Pati, Michael Sheldon, Pulivarthi H. Rao

Research output: Contribution to journalArticle

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Abstract

Osteosarcoma is a primary malignant tumor of bone arising from primitive bone-forming mesenchymal cells and accounts for ∼60% of malignant bone tumors. Our comparative genomic hybridization (CGH) studies have identified frequent amplification at 6p12-p21, 12q13-q15, and 17p11.2 in osteosarcoma. Of these amplified regions, 6p12-p21 is particularly interesting because of its association with progression and poor prognosis in patients with osteosarcoma. In an attempt to identify aberrantly expressed gene(s) mapping to the 6p12-p21 amplicon, a region-specific array was generated using 108 overlapping BAC and P1 clones covering a 28.8-Mb region at 0.26-Mb intervals. Based on array CGH analysis, the 6p amplicon was refined to 7.9 Mb between the clones RP11-91E11 and RP1-244F2 and 10 amplified clones, with possible target genes, were identified. To study the expression pattern of the target genes from the hotspot amplicon and known candidate genes from 6p12-21, we did quantitative reverse transcription-PCR analysis of MAPK14, MAPK13, CDKN1A, PIM1, MDGA1, BTB9, DNAH8, CCND3, PTK7, CDC5L, and RUNX2 on osteosarcoma patient samples and seven cell lines. The combined array CGH and quantitative reverse transcription-PCR analysis identified amplification and overexpression of CDC5L, CCND3, and RUNX2. We screened these three genes for protein expression by Western blotting and immunohistochemistry and detected overexpression of CDC5L. Furthermore, we used an in vivo assay to show that CDC5L possesses potential oncogenic activity. These results indicate that CDC5L, a cell cycle regulator important for the G2-M transition, is the most likely candidate oncogene for the 6p12-p21 amplicon found in osteosarcoma.

Original languageEnglish (US)
Pages (from-to)937-946
Number of pages10
JournalMolecular Cancer Research
Volume6
Issue number6
DOIs
StatePublished - Jun 1 2008

Fingerprint

cdc Genes
Osteosarcoma
Regulator Genes
Comparative Genomic Hybridization
Clone Cells
Bone and Bones
Reverse Transcription
Mitogen-Activated Protein Kinase 14
Genes
Polymerase Chain Reaction
Chromosome Mapping
Oncogenes
Neoplasms
Cell Cycle
Western Blotting
Immunohistochemistry
Gene Expression
Cell Line
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

Lu, X. Y., Lu, Y., Zhao, Y. J., Jaeweon, K., Kang, J., Li, X. N., ... Rao, P. H. (2008). Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma. Molecular Cancer Research, 6(6), 937-946. https://doi.org/10.1158/1541-7786.MCR-07-2115

Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma. / Lu, Xin Yan; Lu, Yaojuan; Zhao, Yi Jue; Jaeweon, Kim; Kang, Jason; Li, Xiao Nan; Ge, Gouqing; Meyer, Rene; Perlaky, Laszlo; Hicks, John; Chintagumpala, Murali; Cai, Wei Wen; Ladanyi, Marc; Gorlick, Richard; Lau, Ching C.; Pati, Debananda; Sheldon, Michael; Rao, Pulivarthi H.

In: Molecular Cancer Research, Vol. 6, No. 6, 01.06.2008, p. 937-946.

Research output: Contribution to journalArticle

Lu, XY, Lu, Y, Zhao, YJ, Jaeweon, K, Kang, J, Li, XN, Ge, G, Meyer, R, Perlaky, L, Hicks, J, Chintagumpala, M, Cai, WW, Ladanyi, M, Gorlick, R, Lau, CC, Pati, D, Sheldon, M & Rao, PH 2008, 'Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma', Molecular Cancer Research, vol. 6, no. 6, pp. 937-946. https://doi.org/10.1158/1541-7786.MCR-07-2115
Lu, Xin Yan ; Lu, Yaojuan ; Zhao, Yi Jue ; Jaeweon, Kim ; Kang, Jason ; Li, Xiao Nan ; Ge, Gouqing ; Meyer, Rene ; Perlaky, Laszlo ; Hicks, John ; Chintagumpala, Murali ; Cai, Wei Wen ; Ladanyi, Marc ; Gorlick, Richard ; Lau, Ching C. ; Pati, Debananda ; Sheldon, Michael ; Rao, Pulivarthi H. / Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma. In: Molecular Cancer Research. 2008 ; Vol. 6, No. 6. pp. 937-946.
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AU - Lu, Xin Yan

AU - Lu, Yaojuan

AU - Zhao, Yi Jue

AU - Jaeweon, Kim

AU - Kang, Jason

AU - Li, Xiao Nan

AU - Ge, Gouqing

AU - Meyer, Rene

AU - Perlaky, Laszlo

AU - Hicks, John

AU - Chintagumpala, Murali

AU - Cai, Wei Wen

AU - Ladanyi, Marc

AU - Gorlick, Richard

AU - Lau, Ching C.

AU - Pati, Debananda

AU - Sheldon, Michael

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