Establishment of a new human osteosarcoma cell line, UTOS-1: cytogenetic characterization by array comparative genomic hybridization

Yasuda, Taketoshi; Koike, Masahiko; Nogami, Shigeharu; Hori, Takeshi; Oya, Takeshi; Suzuki, Kayo; Kimura, Takeshi

doi:10.1186/1756-9966-28-26

Cited by 15 publications

(12 citation statements)

References 44 publications

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“…We [19] and others [42] have previously reported amplification of TOP3A , encoding a type 1 topoisomerase, in osteosarcomas. However no other information about its possible oncogenic potential is available.…”

Section: Discussionmentioning

confidence: 64%

Identification of Novel Candidate Oncogenes in Chromosome Region 17p11.2-p12 in Human Osteosarcoma

Both

Bras

et al. 2012

PLoS ONE

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Osteosarcoma is the most common primary malignancy of bone. The tumours are characterized by high genomic instability, including the occurrence of multiple regions of amplifications and deletions. Chromosome region 17p11.2–p12 is amplified in about 25% of cases. In previous studies, COPS3 and PMP22 have been identified as candidate oncogenes in this region. Considering the complexity and variation of the amplification profiles for this segment, the involvement of additional causative oncogenes is to be expected. The aim of the present investigation is to identify novel candidate oncogenes in 17p11.2–p12. We selected 26 of in total 85 osteosarcoma samples (31%) with amplification events in 17p11.2–p12, using quantitative PCR for 8 marker genes. These were subjected to high-resolution SNP array analysis and subsequent GISTIC analysis to identify the most significantly amplified regions. Two major amplification peaks were found in the 17p11.2–p12 region. Overexpression as a consequence of gene amplification is a major mechanism for oncogene activation in tumours. Therefore, to identify the causative oncogenes, we next determined expression levels of all genes within the two segments using expression array data that could be generated for 20 of the selected samples. We identified 11 genes that were overexpressed through amplification in at least 50% of cases. Nine of these, c17orf39, RICH2, c17orf45, TOP3A, COPS3, SHMT1, PRPSAP2, PMP22, and RASD1, demonstrated a significant association between copy number and expression level. We conclude that these genes, including COPS3 and PMP22, are candidate oncogenes in 17p11.2–p12 of importance in osteosarcoma tumourigenesis.

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Section: Discussionmentioning

confidence: 64%

Identification of Novel Candidate Oncogenes in Chromosome Region 17p11.2-p12 in Human Osteosarcoma

Both

Bras

et al. 2012

PLoS ONE

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“…Fluorescence intensity images were obtained from the hybridized microarray slides using GenoSensor Reader System equipped with Array 300 Software (Vysis-Abbott Japan Inc.) according to the manufacture’s instructions. The total intensity and the intensity ratio of the two dyes for each spot were automatically calculated [7,8]. …”

Section: Methodsmentioning

confidence: 99%

“…The diagnostic cut-off level representing gains and losses of DCNAs was set to 1.15 (upper threshold) and 0.85 (lower threshold), respectively [7,8]. The p value is the probability that the data value for an individual set of target spots is part of the normal distribution.…”

Section: Methodsmentioning

confidence: 99%

Array-based comparative genomic hybridization for genomic-wide screening of DNA copy number alterations in aggressive bone tumors

Koike

Sano

Yasuda

et al. 2012

J Exp Clin Cancer Res

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BackgroundThe genetic pathways of aggressive changes of bone tumors are still poorly understood. It is very important to analyze DNA copy number alterations (DCNAs), to identify the molecular events in the step of progression to the aggressive change of bone tissue.MethodsGenome-wide array-based comparative genomic hybridization (array CGH) was used to investigate DCNAs of 14 samples from 13 aggressive bone tumors, such as giant cell tumors (GCTs) and osteosarcoma (OS), etc.ResultsPrimary aggressive bone tumors had copy number gains of 17.8±12.7% in the genome, and losses of 17.3±11.4% in 287 target clones (threshold for each DCNA: ≦085, 1.15≦). Genetic unstable cases, which were defined by the total DCNAs aberration ≧30%, were identified in 9 of 13 patients (3 of 7 GCTs and all malignant tumors). High-level amplification of TGFβ2, CCND3, WI-6509, SHGC-5557, TCL1A, CREBBP, HIC1, THRA, AFM217YD10, LAMA3, RUNX1 and D22S543, were commonly observed in aggressive bone tumors. On the other hand, NRAS, D2S447, RAF1, ROBO1, MYB, MOS, FGFR2, HRAS, D13S319, D13S327, D18S552, YES1 and DCC, were commonly low. We compared genetic instability between a primary OS and its metastatic site in Case #13. Metastatic lesion showed increased 9 DCNAs of remarkable change (m/p ratio ≧1.3 folds), compared to a primary lesion. D1S214, D1S1635, EXT1, AFM137XA11, 8 M16/SP6, CCND2, IGH, 282 M15/SP6, HIC1 and LAMA3, were overexpressed. We gave attention to HIC1 (17p13.3), which was common high amplification in this series.ConclusionOur results may provide several entry points for the identification of candidate genes associated with aggressive change of bone tumors. Especially, the locus 17p11-13 including HIC1 close to p53 was common high amplification in this series and review of the literature.

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“…1 In addition to such clinical challenges, breakthroughs in medical therapy for this disease continue to be delayed in part because of our poor understanding of its pathogenesis and lack of model systems to study it. Unlike other bone sarcomas that have established in vitro cell lines and xenograft models, 18,26,28,35 there has been little progress in these areas for chordoma. The paucity of cultured chordoma cell lines and lack of their complete characterization has delayed in vitro and in vivo investigation of this cancer.…”

mentioning

confidence: 99%

Generation of chordoma cell line JHC7 and the identification of Brachyury as a novel molecular target

Hsu¹,

Mohyeldin²,

Shah³

et al. 2011

JNS

105

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Object Chordoma is a malignant bone neoplasm hypothesized to arise from notochordal remnants along the length of the neuraxis. Recent genomic investigation of chordomas has identified T (Brachyury) gene duplication as a major susceptibility mutation in familial chordomas. Brachyury plays a vital role during embryonic development of the notochord and has recently been shown to regulate epithelial-to-mesenchymal transition in epithelial-derived cancers. However, current understanding of the role of this transcription factor in chordoma is limited due to the lack of availability of a fully characterized chordoma cell line expressing Brachyury. Thus, the objective of this study was to establish the first fully characterized primary chordoma cell line expressing gain of the T gene locus that readily recapitulates the original parental tumor phenotype in vitro and in vivo. Methods Using an intraoperatively obtained tumor sample from a 61-year-old woman with primary sacral chordoma, a chordoma cell line (JHC7, or Johns Hopkins Chordoma Line 7) was established. Molecular characterization of the primary tumor and cell line was conducted using standard immunostaining and Western blotting. Chromosomal aberrations and genomic amplification of the T gene in this cell line were determined. Using this cell line, a xenograft model was established and the histopathological analysis of the tumor was performed. Silencing of Brachyury and changes in gene expression were assessed. Results The authors report, for the first time, the successful establishment of a chordoma cell line (JHC7) from a patient with pathologically confirmed sacral chordoma. This cell line readily forms tumors in immunodeficient mice that recapitulate the parental tumor phenotype with conserved histological features consistent with the parental tumor. Furthermore, it is demonstrated for the first time that silencing of Brachyury using short hairpin RNA renders the morphology of chordoma cells to a more differentiated-like state and leads to complete growth arrest and senescence with an inability to be passaged serially in vitro. Conclusions This report represents the first xenograft model of a sacral chordoma line described in the literature and the first cell line established with stable Brachyury expression. The authors propose that Brachyury is an attractive therapeutic target in chordoma and that JHC7 will serve as a clinically relevant model for the study of this disease.

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Establishment of a new human osteosarcoma cell line, UTOS-1: cytogenetic characterization by array comparative genomic hybridization

Cited by 15 publications

References 44 publications

Identification of Novel Candidate Oncogenes in Chromosome Region 17p11.2-p12 in Human Osteosarcoma

Identification of Novel Candidate Oncogenes in Chromosome Region 17p11.2-p12 in Human Osteosarcoma

Array-based comparative genomic hybridization for genomic-wide screening of DNA copy number alterations in aggressive bone tumors

Generation of chordoma cell line JHC7 and the identification of Brachyury as a novel molecular target

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