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

Journal of Experimental & Clinical Cancer Research

Kayo Suzuki¹  Takeshi Hori¹  Taketoshi Yasuda¹  Akimi Sano¹  Masahiko Kanamori¹ 

[1] Department of Orthopaedic Surgery, University of Toyama, 2630 Sugitani, Toyama city, Toyama 930-0194, Japan

关键词: Comparative genomic hybridization;    Microarray;    Bone tumors;    Giant cell tumor;    Osteosarcoma;   

Others  :  1136200
DOI  :  10.1186/1756-9966-31-100

 received in 2012-05-02, accepted in 2012-06-25,  发布年份 2012

【 摘 要 】

Background

The 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.

Methods

Genome-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.

Results

Primary 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.

Conclusion

Our 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.

【 授权许可】

   
2012 Kanamori et al.; licensee BioMed Central Ltd.

【 图 表 】

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