RGD Reference Report - Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma. - Rat Genome Database

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

Authors: Lu, XY  Lu, Y  Zhao, YJ  Jaeweon, K  Kang, J  Xiao-Nan, L  Ge, G  Meyer, R  Perlaky, L  Hicks, J  Chintagumpala, M  Cai, WW  Ladanyi, M  Gorlick, R  Lau, CC  Pati, D  Sheldon, M  Rao, PH 
Citation: Lu XY, etal., Mol Cancer Res. 2008 Jun;6(6):937-46. doi: 10.1158/1541-7786.MCR-07-2115.
RGD ID: 10047050
Pubmed: PMID:18567798   (View Abstract at PubMed)
PMCID: PMC2693718   (View Article at PubMed Central)
DOI: DOI:10.1158/1541-7786.MCR-07-2115   (Journal Full-text)

Osteosarcoma is a primary malignant tumor of bone arising from primitive bone-forming mesenchymal cells and accounts for approximately 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
osteosarcoma  IAGP 10047050DNA:amplification:cds (human)RGD 
osteosarcoma  ISOCDC5L (Homo sapiens)10047050; 10047050DNA:amplification:cds (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cdc5l  (cell division cycle 5-like)

Genes (Mus musculus)
Cdc5l  (cell division cycle 5-like)

Genes (Homo sapiens)
CDC5L  (cell division cycle 5 like)


Additional Information