| 1. |
- Hallor, Karolin H, et al.
(författare)
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Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors.
- 2009
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 15:8, s. 2685-2694
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: 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. EXPERIMENTAL DESIGN: The overall pattern of genomic imbalances was assessed in a series of 67 chondrosarcomas using array comparative genomic hybridization. Statistical analyses were applied to evaluate the significance of alterations detected in subgroups based on clinical data, morphology, grade, tumor size, and karyotypic features. Also, the global gene expression profiles were obtained in a subset of the tumors. RESULTS: Genomic imbalances, in most tumors affecting large regions of the genome, were found in 90% of the cases. Several apparently distinctive aberrations affecting conventional central and peripheral tumors, respectively, were identified. 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. The chromosomal imbalances in two distinct groups of predominantly near-haploid and near-triploid tumors, respectively, support the notion that polyploidization of an initially hyperhaploid/hypodiploid cell population is a common mechanism of chondrosarcoma progression. Increasing patient age as well as tumor grade were associated with adverse outcome, but no copy number imbalance affected metastasis development or tumor-associated death. CONCLUSION: Despite similarities in the overall genomic patterns, the present findings suggest that some regions are specifically altered in conventional central and peripheral tumors, respectively.
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| 2. |
- Hallor, Karolin H, et al.
(författare)
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Two genetic pathways, t(1;10) and amplification of 3p11-12, in myxoinflammatory fibroblastic sarcoma, haemosiderotic fibrolipomatous tumour, and morphologically similar lesions.
- 2009
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 217, s. 716-727
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Tidskriftsartikel (refereegranskat)abstract
- Myxoinflammatory fibroblastic sarcoma (MIFS) is a low-grade malignant neoplasm for which limited genetic information, including a t(1;10)(p22;q24) and amplification of chromosome 3 material, is available. To further characterize these aberrations, we have investigated eight soft tissue sarcomas diagnosed as MIFS, haemosiderotic fibrolipomatous tumour (HFT), myxoid spindle cell/pleomorphic sarcoma with MIFS features, and inflammatory malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma with prominent inflammation (IMFH) harbouring a t(1;10) or variants thereof and/or ring chromosomes with possible involvement of chromosome 3. Using chromosome banding, fluorescence in situ hybridization, array-based comparative genomic hybridization, global gene expression, and real-time quantitative PCR analyses, we identified the breakpoint regions on chromosomes 1 and 10, demonstrated and delineated the commonly amplified region on chromosome 3, and assessed the consequences of these alterations for gene expression. The breakpoints in the t(1;10) mapped to TGFBR3 in 1p22 and in or near MGEA5 in 10q24, resulting in transcriptional up-regulation of NPM3 and particularly FGF8, two consecutive genes located close to MGEA5. The ring chromosomes contained a commonly amplified 1.44 Mb region in 3p11-12, which was associated with increased expression of VGLL3 and CHMP2B. The identified genetic aberrations were not confined to MIFS; an identical t(1;10) was also found in a case of HFT and the amplicon in 3p was seen in an IMFH. Copyright (c) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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| 3. |
- Hansén Nord, Karolin, et al.
(författare)
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Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation.
- 2008
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 98:2, s. 434-442
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Tidskriftsartikel (refereegranskat)abstract
- The initiating somatic genetic events in chordoma development have not yet been identified. Most cytogenetically investigated chordomas have displayed near-diploid or moderately hypodiploid karyotypes, with several numerical and structural rearrangements. However, no consistent structural chromosome aberration has been reported. This is the first array-based study characterising DNA copy number changes in chordoma. Array comparative genomic hybridisation (aCGH) identified copy number alterations in all samples and imbalances affecting 5 or more out of the 21 investigated tumours were seen on all chromosomes. In general, deletions were more common than gains and no high-level amplification was found, supporting previous findings of primarily losses of large chromosomal regions as an important mechanism in chordoma development. Although small imbalances were commonly found, the vast majority of these were detected in single cases; no small deletion affecting all tumours could be discerned. However, the CDKN2A and CDKN2B loci in 9p21 were homo- or heterozygously lost in 70% of the tumours, a finding corroborated by fluorescence in situ hybridisation, suggesting that inactivation of these genes constitute an important step in chordoma development.British Journal of Cancer (2008) 98, 434-442. doi:10.1038/sj.bjc.6604130 www.bjcancer.com Published online 11 December 2007.
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