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| 2. |
- Zirn, B, et al.
(author)
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Expression profiling of Wilms tumors reveals new candidate genes for different clinical parameters
- 2006
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In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 118:8, s. 1954-1962
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Journal article (peer-reviewed)abstract
- Wilms tumor is the most frequent renal neoplasm in children, but our understanding of its genetic basis is still limited. We performed cDNA microarray experiments using 63 primary Wilms tumors with the aim of detecting new candidate genes associated with malignancy grade and tumor progression. All tumors had received preoperative chemotherapy as mandated by the SIOP protocol, which sets this study apart from related approaches in the Unites States that are based on untreated samples. The stratification of expression data according to clinical criteria allowed a rather clear distinction between different subsets of Wilms tumors. Clear-cut differences in expression patterns were discovered between relapse-free as opposed to relapsed tumors and tumors with intermediate risk as opposed to high risk histology. Several differentially expressed genes, e.g. TRIM22, CENPF, MYCN, CTGF, RARRES3 and EZH2, were associated with Wilms tumor progression. For a subset of differentially expressed genes, microarray data were confirmed by real-time RT-PCR on the original set of tumors. Interestingly, we found the retinoic acid pathway to be deregulated at different levels in advanced tumors suggesting that treatment of these tumors with retinoic acid may represent a promising novel therapeutic approach. (c) 2005 Wiley-Liss, Inc.
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| 3. |
- Fortuna, E., et al.
(author)
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Properties of co-deposited layers on graphite high heat flux components at the TEXTOR tokamak
- 2007
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In: Journal of Nuclear Materials. - : Elsevier. - 0022-3115 .- 1873-4820. ; 367:B, s. 1507-1511
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Journal article (peer-reviewed)abstract
- The objective of this work was to examine the structure, composition and properties of co-deposited films from the TEXTOR tokamak. Hydrogenated films formed on the toroidal belt pump limiter (ALT-II), and on the ICRF antenna grill were studied using a set of material analysis techniques. Plasma edge diagnostics were used to assess the parameters influencing the film formation during discharges auxiliary heated by ICRF. The essential results are summarized as follows: (i) the distribution of plasma impurities co-deposited in the films is non-uniform and (ii) the surface topography, crystallographic structure, fuel retention and composition (i.e., content of re-deposited plasma impurities) of the films show significant diversity depending on the location where they were formed. These differences are associated with the local geometry, the tokamak operation scenarios and the resulting plasma edge properties.
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| 4. |
- Matthews, G. F., et al.
(author)
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Overview of the ITER-like wall project
- 2007
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In: Physica Scripta. - 0031-8949 .- 1402-4896. ; T128, s. 137-143
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Journal article (peer-reviewed)abstract
- Work is in progress to completely replace, in 2008/9, the existing JET CFC tiles with a configuration of plasma facing materials consistent with the ITER design. The ITER-like wall (ILW) will be created with a combination of beryllium ( Be), tungsten ( W), W-coated CFC and Be-coated inconel tiles, with the material depending on the local anticipated heat flux and geometry. It is part of an integrated package of JET enhancements whose aim is to develop an understanding of the ITER materials issues and develop the techniques required to operate with inductive and advanced scenarios as close as possible to ITER parameters. Over 4000 tiles will be replaced and the ILW will accommodate additional heating up to at least 50 MW for 10 s. This paper describes the scientific background to the project, the technical objectives, the material configuration selected, the R&D behind the practical realization of the objectives and the generic problems associated with the Be tiles ( power handling capacity and disruption induced eddy currents). One of the objectives is to maintain or improve the existing CFC tile power handling performance which has been achieved in most cases by hiding bolt holes, optimizing tile size and profile and introducing castellations on plasma facing surfaces.
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| 5. |
- Downs-Kelly, Erinn, et al.
(author)
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The utility of fluorescence in situ hybridization (FISH) in the diagnosis of myxoid soft tissue neoplasms
- 2008
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In: American Journal of Surgical Pathology. - 1532-0979. ; 32:1, s. 8-13
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Journal article (peer-reviewed)abstract
- Diagnosing myxoid soft tissue neoplasms can be challenging because of overlapping histologic features. Distinct chromosomal translocations have been identified in several myxoid sarcomas, including t(12;16)(q13;p11) FUS-DDIT3 in myxoid liposarcoma, t(7,-16)(q34;p11) FUS-CREB3L2 in low-grade fibromyxoid sarcoma, and t(9;22)(q31;q12) EWSRINR4A3 in extraskeletal myxoid chondrosarcoma. These recurrent chromosomal alterations are attractive targets for diagnostic studies. To that end, dual-color, break-apart fluorescence in situ hybridization (FISH) probes spanning the genomic regions of EWSRI (22q12), DDIT3 (12q13), and FUS (16p11) (Vysis, Downer's Grove, IL) were evaluated in formalin-fixed, paraffin-embedded tissues from myxoid neoplasms, including intramuscular myxoma (it 10), myxoid liposarcoma (n = 18) low-grade fibromyxoid sarcoma (n = 10), extraskeletal myxoid chondrosarcoma (n = 13), and myxofibrosarcoma (n = 8). Of the myxoid liposarcomas, 18/18 cases had a rearrangement of the DDIT3 gene, with 17/18 (94.4%) showing both DDIT3 and FUS gene rearrangements. A FUS gene rearrangement was identified in 7/10 (70%) of lowgrade fibromyxoid sarcomas, with no changes involving EWSRI or DDIT3. An EWSRI translocation was seen in 6/13 (46.2%) of extraskeletal myxoid chondrosarcomas, without changes in DDIT3 or FUS genes. The remaining neoplasms studied showed no rearrangements involving DDIT3, FUS, or EWSRI genes. In conclusion, interphase FISH using DDIT3 and FUS probes identifies the characteristic translocation in myxoid liposarcoma. FUS and EWSRI probes are useful in confirming the diagnosis of low-grade fibromyxoid sarcoma and extraskeletal myxoid chondrosarcoma, respectively. The specificity of the probes is documented as none of the non-translocation-associated myxoid tumors showed genomic abnormalities with the probes tested. FISH is capable of providing specific ancillary information useful in this often difficult differential diagnosis.
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| 6. |
- Hallor, Karolin Hansén, et al.
(author)
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Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma
- 2005
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In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 44:1, s. 97-102
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Journal article (peer-reviewed)abstract
- Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor that usually occurs in children and young adults. Only two cases of AFH with genetic rearrangements have been reported previously; both of these had a FUS-ATF1 fusion gene. We have studied an AFH from a 9-year-old boy whose tumor displayed a t(12;22)(q13;q12) as the sole cytogenetic aberration. FISH,RT-PCR, and sequence analyses revealed an EWSR1-ATF1 fusion gene that has previously been reported in clear cell sarcoma (CCS), a soft tissue sarcoma that is morphologically and clinically distinct from AFH. This study thus has demonstrated that the EWSR1-ATF1 chimera represents a fusion gene that can be associated with different tumor types. Simultaneous expression of the EWSR1-ATF1 and MITF-M transcripts in CCS has led to the proposal that the MITF-M promoter is transactivated by EWSR1-ATF1. The AFH, however, did not express the MITF-M transcript, supporting the theory that MITF-M expression in CCS is a reflection of its cellular origin, rather than a consequence of the presence of an EWSR1-ATF1 fusion protein. Activation of the EWSR1-ATF1 oncogene is probably an early step in the transformation process, but the overall gene expression patterns are likely to vary considerably between AFH and CCS, in keeping with their clinicopathologic differences.
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| 7. |
- Hallor, Karolin H, et al.
(author)
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Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors.
- 2009
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In: Clinical Cancer Research. - 1078-0432. ; 15:8, s. 2685-2694
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Journal article (peer-reviewed)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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| 8. |
- Hallor, Karolin H, et al.
(author)
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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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In: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 217, s. 716-727
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Journal article (peer-reviewed)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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| 9. |
- Hansén Nord, Karolin, et al.
(author)
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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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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 98:2, s. 434-442
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Journal article (peer-reviewed)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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| 10. |
- Hansén Nord, Karolin, et al.
(author)
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Fusion genes in angiomatoid fibrous histiocytoma
- 2007
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In: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 251:1, s. 158-163
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Journal article (peer-reviewed)abstract
- Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of low malignant potential and uncertain differentiation. Only three genetically investigated cases of AFH have been reported. Two of them displayed a FUS-ATF1 fusion gene and one showed an EWSR1-ATF1 chimera. Using RT-PCR analysis, we have identified the EWSR1-ATF1 fusion transcript, and delineated the genomic breakpoints, in two new cases of AFH. Previously, the EWSR1-ATF1 fusion protein has been suggested to activate expression of the MITF-M transcript, and therefore the expression pattern of the MITF gene was studied. The MITF-M transcript was not detected in either AFH, in line with the finding that the co-activator SOX10 was not expressed. Thus, of the five AFH that have been molecularly analyzed to date, two have displayed a FUS-ATF1 fusion gene and three have shown an EWSR1-ATF1 chimera. There is no apparent correlation between the type of fusion gene and clinicopathologic features. Nonetheless, RT-PCR for these fusion transcripts remains a valuable diagnostic adjunct in the distinction between AFH and other soft tissue tumors or metastases that may simulate it.
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