Genome-wide array comparative genomic hybridization analysis reveals distinct amplifications in osteosarcoma

Man, Tsz-Kwong; Lu, Xin; Kim, Jaeweon; Perlaky, László; Harris, Chad; Shah, Shishir K.; Ladanyi, Marc; Görlick, Richard; Lau, Ching C.; Rao, Pulivarthi H.

doi:10.1186/1471-2407-4-45

Cited by 132 publications

(110 citation statements)

References 25 publications

(24 reference statements)

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“…Recently, others and we have identified several chromosomal regions that are recurrently amplified in osteosarcoma by chromosomal comparative genomic hybridization (CGH) and array-based CGH (2)(3)(4)(5)(6)(7)(8)10). Of these, amplification of 6p12-p21 and 17p11.2 appeared to be markers of an early genetic change in osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

Cell Cycle Regulator GeneCDC5L, a Potential Target for 6p12-p21 Amplicon in Osteosarcoma

Lu²,

Zhao³

et al. 2008

Molecular Cancer Research

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Osteosarcoma is a primary malignant tumor of bone arising from primitive bone-forming mesenchymal cells and accounts for f60% 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 G 2 -M transition, is the most likely candidate oncogene for the 6p12-p21 amplicon found in osteosarcoma. (Mol Cancer Res 2008;6(6):937 -46)

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Section: Introductionmentioning

confidence: 99%

Cell Cycle Regulator GeneCDC5L, a Potential Target for 6p12-p21 Amplicon in Osteosarcoma

Lu²,

Zhao³

et al. 2008

Molecular Cancer Research

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“…Comparative genomic hybridization (CGH) on ordered BAC-Arrays provides a high throughput, high resolution screening method that can be used to quantitatively measure DNA copy number aberrations in solid tumors, and map such alterations directly on the genome This method of genome scanning has been used to search for genomic regions frequently involved in producing solid tumors including breast, colon, brain, esophagus, and kidney [11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

aCGH local copy number aberrations associated with overall copy number genomic instability in colorectal cancer: Coordinate involvement of the regions including BCR and ABL

Bartos

Gaile

McQuaid

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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In order to identify small regions of the genome whose specific copy number alteration is associated with high genomic instability in the form of overall genome-wide copy number aberrations, we have analyzed array-based comparative genomic hybridization (aCGH) data from 33 sporadic colorectal carcinomas. Copy number changes of a small number of specific regions were significantly correlated with elevated overall amplifications and deletions scattered throughout the entire genome. One significant region at 9q34 includes the c-ABL gene Another region spanning 22q11-13 includes the breakpoint cluster region (BCR) of the Philadelphia chromosome Coordinate 22q11-13 alterations were observed in nine of eleven tumors with the 9q34 alteration Additional regions on 1q and 14q were associated with overall genome-wide copy number changes, while copy number aberrations on chromosome 7p, 7q, and 13q21.1-31.3 were found associated with this instability only in tumors from patients with a smoking history Our analysis demonstrates there are a small number of regions of the genome where gain or loss is commonly associated with a tumor's overall level of copy number aberrations Our finding BCR and ABL located within two of the instability-associated regions, and the involvement of these two regions occurring coordinately, suggests a system akin to the BCR-ABL translocation of CML may be involved in genomic instability in about one-third of human colorectal carcinomas.

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“…This represents a paradigm shift in drug development as this drug was approved based on a tumor biomarker rather than the tumor type or organ of origin. In sarcoma research, Man et al have reported the first application of array-based comparative genomic hybrid ization (aCGH) in osteosarcoma, which identified distinct amplifications and deletions that represent potential therapeutic targets [15] . Similarly, using aCGH and expression arrays, Savola et al have identified important copy number aberrations (CNAs) in Ewing sarcoma and correlated the number of CNAs in the tumor to patient's survival [16] .…”

Section: Dna Mutation and Copy Number Analysismentioning

confidence: 99%

The advancements of genomics and data integration in sarcoma research

et al. 2017

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Abstract:In the age of big data, genomics and clinical research have reached a crossroads. A wealth of data is being generated, but it is becoming increasingly complicated to analyze these data to extract meaningful results. The ability to understand biological systems holistically has unprecedented potential to transform how cancers are treated. Recent major advances leading biomedical research towards "systems medicine" have been fueled by high-throughput platforms, such as microarrays and next-generation sequencing, which can capture vast amounts of data in different genomic spaces. Unfortunately, because of high dimensionality and complex relationships among these data, inferring comprehensive and useful biological models has proven computationally and statistically challenging. However, novel bioinformatic methods for data integration of cancer genomic datasets have been developed. In this review, we will describe the applications of various genomic approaches in sarcoma research and introduce bioinformatic methods for data integration. With the continuing evolution of technological and bioinformatic methodologies, the application of big data within clinics and hospitals will ultimately result in significant improvements on how cancers are detected and treated.Keywords: omics; genomics; sarcomas; sequencing; microarray; data integration; bioinformatics; big data

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Genome-wide array comparative genomic hybridization analysis reveals distinct amplifications in osteosarcoma

Cited by 132 publications

References 25 publications

Cell Cycle Regulator GeneCDC5L, a Potential Target for 6p12-p21 Amplicon in Osteosarcoma

Cell Cycle Regulator GeneCDC5L, a Potential Target for 6p12-p21 Amplicon in Osteosarcoma

aCGH local copy number aberrations associated with overall copy number genomic instability in colorectal cancer: Coordinate involvement of the regions including BCR and ABL

The advancements of genomics and data integration in sarcoma research

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