Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors (BAC/CGH)

ABSTRACT: DNA copy number analysis of 67 fresh frozen chondrosarcoma biopsies using 32k BAC and 244k oligo array CGH. Genomic imbalances, in most tumors affecting large regions of the genome, were found in 90% of the cases. Although rare, recurrent amplifications were found at 8q24.21-q24.22 and 11q22.1-q22.3, and homozygous deletions of loci previously implicated in chondrosarcoma development affected the CDKN2A, EXT1 and EXT2 genes. Keywords: chondrosarcoma, array comparative genomic hybridization DNA copy number analysis was performed using tiling microarrays containing more than 32,000 partly overlapping BAC clones, generating complete coverage of the Homo sapiens genome. The arrays were produced at the Swegene DNA Microarray Resource Center, Department of Oncology, Lund University (http://swegene.onk.lu.se), using BAC clones mapped to the hg17 genome build. Male genomic DNA (Promega) was used as reference. In five cases (cases 2, 4, 34, 36, and 67) the DNA copy number status was assessed by oligo microarrays containing ~236,000 oligonucleotide probes (Agilent, Palo Alto, CA, USA). These samples were hybridized against gender-matched reference DNA.

ORGANISM(S): Homo sapiens

SUBMITTER: Karolin Nord

PROVIDER: E-GEOD-12439 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors.

Hallor Karolin H KH Staaf Johan J Bovée Judith V M G JV Hogendoorn Pancras C W PC Cleton-Jansen Anne-Marie AM Knuutila Sakari S Savola Suvi S Niini Tarja T Brosjö Otte O Bauer Henrik C F HC Vult von Steyern Fredrik F Jonsson Kjell K Skorpil Mikael M Mandahl Nils N Mertens Fredrik F

Clinical cancer research : an official journal of the American Association for Cancer Research 20090331 8

<h4>Purpose</h4>Histologic grade is currently the best predictor of clinical course in chondrosarcoma patients. Grading suffers, however, from extensive interobserver variability and new objective markers are needed. Hence, we have investigated DNA copy numbers in chondrosarcomas with the purpose of identifying markers useful for prognosis and subclassification.<h4>Experimental design</h4>The overall pattern of genomic imbalances was assessed in a series of 67 chondrosarcomas using array compara ...[more]

PMID: 19336518

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Project description:DNA copy number analysis of myxoinflammatory fibroblastic sarcomas, and related lesions, using 32k BAC array CGH. All four cases analyzed with array CGH showed amplification of the region 86.30-87.74 Mb in 3p11.1-12.1. No additional aberration was detected in more than two tumors, except for the deletion distal to the amplification on chromosome 3. Case 1 showed deletion affecting the region from the centromere of chromosome 1 to the 5'-end of TGFBR3. Homozygous deletion was found in one case (case 6) affecting the region 21.08-22.15 Mb on chromosome arm 9p harboring the CDKN2A and CDKN2B genes. DNA copy numbers in cases 1 and 6-8 were analyzed using tiling microarrays containing more than 32 000 partly overlapping BAC clones, generating complete coverage of the human genome (JÃ¶nsson et al., 2007, Genes Chromosomes Cancer 46: 543-58.). The arrays were produced at the Swegene DNA Microarray Resource Center, Department of Oncology, Lund University (http://swegene.onk.lu.se), as previously described (JÃ¶nsson et al., 2007), using BAC clones mapped to the hg17 genome build. Extraction, labeling and hybridization of genomic DNA from freshly frozen tumor biopsies, as well as pretreatment and washing of slides were performed as described (Heidenblad et al., 2006, Oncogene 25: 7106-16). As a control for normal copy number, a DNA pool derived from multiple healthy male donors was used (Promega, Madison, WI, USA). Primary array CGH data were collected using the GenePix Pro 4.0 (Axon Instruments Inc., Foster City, CA, USA). The quantified data matrix was deposited into the web-based database BioArray Software Environment (BASE) (Saal et al., 2002, Genome Biol 3: software0003.1-0003.6), and data analyses were done as described (Hallor et al., 2008, Br J Cancer 98: 434-42). In brief, following background correction the log(2) ratios were calculated for each spot, and unreliable features and spots not showing signal-to-noise ratios ?5 for both channels were eliminated. Normalization of data was performed using pin-based Lowess normalization and single outlier probes were removed. Thereafter, the log(2) ratios for each sample were segmented, followed by elimination of segments less than 500 kb in size. Copy number alterations were determined by comparing the segmented log(2) ratios to gain/loss thresholds obtained by an adaptive scaling method (Staaf et al., 2007, BMC Genomics 8: 382).

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Dataset Information

Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors (BAC/CGH)

Publications

Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors.

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