Genomic gains of COLIAI-PDFGB occur in the histologic evolution of giant cell fibroblastoma into dermatofibrosarcoma protuberans

CIPAX, Medicina Diagnostica, Sao Jose dos Campos SP, Brazil.
Genes Chromosomes and Cancer (Impact Factor: 4.04). 03/2008; 47(3):260-5. DOI: 10.1002/gcc.20530
Source: PubMed


Giant cell fibroblastoma (GCF) is a subcutaneous mesenchymal neoplasm characterized by the chromosomal t(17;22), which results in the formation of the fusion gene COL1A1-PDGFB. This same fusion gene is also seen in the supernumerary ring chromosome of dermatofibrosarcoma protuberans (DFSP). Several studies have addressed the molecular genetics of DFSP but molecular cytogenetic characterization of individual areas and cell components in pure GCF and GCF/DFSP hybrids have not been performed. Herein, we studied the frequency and genomic copy number of COL1A1-PDGFB in pure GCF and GCF/DFSP hybrids, and identified the molecular cytogenetic signatures in individual cells in each component. Four pure GCF and nine GCF/DFSP hybrids were studied. All tumors exhibited classical histological features and CD34 expression. COL1A1 and PDGFB rearrangements were evaluated by fluorescence in situ hybridization (FISH) using probes for COL1A1 and PDGFB on paraffin-embedded thin tissue sections. All GCF and GCF/DFSP hybrids showed unbalanced rearrangements of COL1A1-PDGFB at the molecular cytogenetic level. Genomic gains of COL1A1-PDGFB were found predominantly in the DFSP component of GCF/DFSP hybrids but in none of the pure GCF, suggesting that these gains are associated with the histologic evolution of GCF into DFSP. The molecular cytogenetic abnormalities were found not only in the spindle/stellated cells but also in individual nuclei of the multinucleated giant cells, suggesting that these cells may result from the fusion of individual neoplastic cells.

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    • "Currently, commercial FISH probes are available, e.g., ZytoLight-SPEC COL1A1-PDGFB Dual Color Dual Fusion Probe (ZytoVision GmbH, Bremerhaven, Germany) (47). Different methods, such as Southern blot analysis, RT-PCR and FISH, based on frozen tissue specimens or using archival FFPE tumor samples have shown that COL1A1/PDGFB chimeric genes are present in all cases of DFSP (43,48,49). "
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    ABSTRACT: Approximately one third of soft tissue tumors are characterized by chromosomal aberrations, in particular, translocations and amplifications, which appear to be highly specific. The identification of fusion transcripts not only supports the diagnosis, but provides the basis for the development of novel therapeutic strategies aimed at blocking the aberrant activity of chimeric proteins. Molecular biology, and in particular, cytogenetic and qualitative and quantitative polymerase chain reaction technologies, allow with high efficiency and specificity, the determination of specific fusion transcripts resulting from chromosomal translocations, as well as the analysis of gene amplifications. In this review, various molecular techniques that allow the identification of translocations and consequent fusion transcripts generated are discussed in the broad spectrum of soft tissue tumors.
    International Journal of Molecular Medicine 04/2014; 33(6). DOI:10.3892/ijmm.2014.1726 · 2.09 Impact Factor
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    • "In our previous experience (Llombart et al., accepted for publication), we observed that 76% is detected using RT-PCR in paraffin embedded tissue samples. FISH has been performed using both PDGFB break-apart and COL1A1/PDGFB dual color dual fusion (DCDF) non-commercial probe strategies (Abbott et al., 2006; Craver et al., 2006; Maire et al., 2007; Macarenco et al., 2008; Patel et al., 2008; Segura et al., 2011). It has been postulated that dual fusion probes are better than break-apart regarding sensitivity because their false positive rate in normal tissues is very low (Ventura et al., 2006). "
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    ABSTRACT: Dermatofibrosarcoma protuberans (DFSP) is characterized by the presence of the t(17;22)(q22;q13) that leads to the fusion of the COL1A1 and PDGFB genes. This translocation can be detected by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH) techniques. We have evaluated the usefulness of a dual color dual fusion FISH probe strategy for COL1A1/PDGFB detection in a series of 103 archival DFSPs and compared the obtained results with RT-PCR analyses. FISH and RT-PCR were carried out on paraffin embedded tissue samples. Regarding the RT-PCR approach, all COL1A1 exons and exon 2 of PDGFB were evaluated. Sensitivity, specificity, positive and negative predictive values were assessed considering the histological diagnosis as the gold standard. We also analyzed the relationship between the genetic findings and the clinicopathological variables of the tumors. The COL1A1/PDGFB translocation was detected in 93% of DFSP. Both techniques showed a similar specificity (100%), but FISH was more sensitive than RT-PCR (90% vs. 72%). Regarding, clinicopathological features, a higher percentage of positive cells detected by FISH was significantly associated with the fibrosarcomatous DFSP variant (P < 0.001). Interestingly, all CD34 negative DFSP (n = 5) were positive for COL1A1/PDGFB translocation by both techniques. In conclusion, the majority of DFSP harbor the COL1A1/PDGFB translocation and FISH technique should be recommended as a routine diagnostic tool, especially in cases showing unusual histopathological subtypes and/or immunohistochemical features.
    Genes Chromosomes and Cancer 07/2011; 50(7):510-7. DOI:10.1002/gcc.20874 · 4.04 Impact Factor
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    • "Most of the cases studied showed multiple copies of the fusion gene. This finding has been observed in previous studies [17] [19] [21] [26]. Abbott el al [19] "
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    ABSTRACT: Dermatofibrosarcoma protuberans is genetically characterized by the translocation t(17;22)(q22;q13) resulting in the PDGFB/COL1A1 fusion gene. Fluorescence in situ hybridization with specific probes enables a rapid detection of this gene. In this study, the presence of the translocation t(17;22)(q22;q13) by fluorescence in situ hybridization in paraffin-embedded tissue microarrays was analyzed. Two tissue microarrays including 40 cases of dermatofibrosarcoma protuberans and 20 dermatofibromas were evaluated. Fluorescence in situ hybridization analyses were performed using a dual-color dual-fusion noncommercial probe. Clinical and histopathologic features were examined, and the association with fluorescence in situ hybridization results was assessed. A total of 29 samples of dermatofibrosarcoma protuberans and 16 of dermatofibromas were successfully evaluated. Twenty-five (86%) dermatofibrosarcoma protuberans samples were positive for the translocation, which was absent in all samples of dermatofibromas. Two of the negative dermatofibrosarcoma protuberans showed unusual, hypercellular areas with marked cytologic atypia, whereas 1 case exhibited overlap features with dermatofibroma. Tumors with fibrosarcomatous areas seemed to have a higher percentage of positive cells and the number of copies of the COL1A1/PDFGB gene. In conclusion, the COL1A1/PDGFB fusion gene was present in most of the dermatofibrosarcoma protuberans tissue samples. The detection of the translocation may be an additional diagnostic tool in cases of dermatofibrosarcoma protuberans showing nonconclusive histologic features.
    Human pathology 02/2011; 42(2):176-84. DOI:10.1016/j.humpath.2010.07.015 · 2.77 Impact Factor
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