Sustained complete remission of metastatic dermatofibrosarcoma protuberans with imatinib mesylate

Labropoulos, Stefanos; Fletcher, Jonathan A.; Oliveira, André M.; Papadopoulos, Savvas; Razis, Evangelia

doi:10.1097/00001813-200504000-00014

Cited by 92 publications

(65 citation statements)

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“…25,26 The role of PDGFB activation in imatinib responsiveness has not been investigated, but it is possible that the subset of fibrosarcomatous dermatofibrosarcoma protuberans that operate with gains of COL1A1-PDGFB may be more susceptible to imatinib. 24 However, our data also clearly indicate that additional genetic factors such as gains of TP53 mutations play an important role in tumor behavior. 2 Therefore, investigation of other oncogenic mechanisms in the PDGFB-PDGFRB signaling pathway is necessary.…”

Section: Discussionmentioning

confidence: 58%

“…Inhibitors of PDGFB such as imatinib mesylate have been shown to have activity against primary and metastatic dermatofibrosarcoma protuberans and fibrosarcomatous dermatofibrosarcoma protuberans in small trials. [23][24][25] In contrast, a small subset of dermatofibrosarcoma protuberans patients have shown transient or partial responses to imatinib. 25,26 The role of PDGFB activation in imatinib responsiveness has not been investigated, but it is possible that the subset of fibrosarcomatous dermatofibrosarcoma protuberans that operate with gains of COL1A1-PDGFB may be more susceptible to imatinib.…”

Section: Discussionmentioning

confidence: 99%

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Gains of COL1A1-PDGFB genomic copies occur in fibrosarcomatous transformation of dermatofibrosarcoma protuberans

et al. 2006

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Dermatofibrosarcoma protuberans is a superficial low-grade sarcoma that rarely evolves into a high-grade fibrosarcoma. Dermatofibrosarcoma protuberans is genetically characterized by the unbalanced chromosomal t(17;22)(q21;q13), usually in the form of a supernumerary ring chromosome. The product of this chromosomal translocation is the chimeric gene COL1A1-PDGFB (collagen type I alpha I-platelet-derived growth factor beta), which is amplified at low levels in the ring chromosome. The aims of this study were to evaluate (1) whether genomic gains of this fusion gene occur during the clonal evolution of dermatofibrosarcoma protuberans into fibrosarcomatous dermatofibrosarcoma protuberans and (2) whether there is a difference between the number of genomic copies of COL1A1-PDGFB between classic dermatofibrosarcoma protuberans and dermatofibrosarcoma protuberans areas associated with fibrosarcomatous dermatofibrosarcoma protuberans. Eleven cases of fibrosarcomatous dermatofibrosarcoma protuberans with both dermatofibrosarcoma protuberans and fibrosarcomatous areas and 10 cases of classic dermatofibrosarcoma protuberans were studied. Genomic copies of COL1A1-PDGFB were evaluated by fluorescence in situ hybridization using a custom designed probe for the PDGFB locus on 4 lm thick paraffin-embedded tissue sections. Genomic gains of the COL1A1-PDGFB gene were observed in six (of 10) fibrosarcomatous dermatofibrosarcoma protuberans in the fibrosarcomatous areas when compared to the dermatofibrosarcoma protuberans areas of the same tumor (2-7 gene copies (median PDGFB copy gain, 2.8) versus 1-3 gene copies (median PDGFB copy gain, 1.7), respectively, P ¼ 0.004). Four fibrosarcomatous dermatofibrosarcoma protuberans did not show genomic gains of COL1A1-PDGFB fusion gene between the two areas. Essentially no difference in the copy number of COL1A1-PDGFB fusion gene was observed between dermatofibrosarcoma protuberans areas of classic dermatofibrosarcoma protuberans and dermatofibrosarcoma protuberans areas of fibrosarcomatous dermatofibrosarcoma protuberans (median PDGFB copy gain of 1.8 versus 1.7, respectively, P ¼ 0.36). Genomic gains of COL1A1-PDGFB fusion gene is possibly an oncogenic mechanism that is identified in the clonal evolution of a subset of dermatofibrosarcoma protuberans that evolves into fibrosarcomatous dermatofibrosarcoma protuberans. Since this finding was not observed in all cases of fibrosarcomatous dermatofibrosarcoma protuberans, other oncogenic mechanisms may be operating in this form of tumor progression. Copy number of COL1A1-PDGFB fusion gene in the classic dermatofibrosarcoma protuberans areas does not seem to be a major predisposing mechanism for fibrosarcomatous transformation.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Gains of COL1A1-PDGFB genomic copies occur in fibrosarcomatous transformation of dermatofibrosarcoma protuberans

et al. 2006

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“…Recently, a limited number of clinical reports have suggested that imatinib, a potent and specific inhibitor of several protein-tyrosine kinases, including PDGFRB, can induce regression in patients with unresectable, recurrent, or metastatic dermatofibrosarcoma protuberans. [3][4][5][6] Maki et al 3 …”

Section: Pdgfb and Pdgfrb Mrna Expressionmentioning

confidence: 99%

“…Recently, patients with unresectable dermatofibrosarcoma protuberans have been reported to be successfully treated with imatinib, a potent and specific inhibitor of several protein-tyrosine kinases, including PDGFRB. [3][4][5][6] Accordingly, both generations of the COL1A1-PDGFB fusion transcripts and their downstream PDGFB/PDGFRB signaling pathway are considered to play an important role in tumorigenesis and treatment of dermatofibrosarcoma protuberans. In this study, we detected the fusion gene transcripts and quantified the PDGFB gene amplification and PDGFB/PDGFRB mRNA levels by using a real-time polymerase chain reaction (PCR) system.…”

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confidence: 99%

Detection of COL1A1-PDGFB fusion transcripts and PDGFB/PDGFRB mRNA expression in dermatofibrosarcoma protuberans

et al. 2007

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Fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor beta chain (PDGFB) gene has been described in dermatofibrosarcoma protuberans. The abnormal fusion transcripts probably cause PDGFB and its receptor (platelet-derived growth factor receptor beta, PDGFRB) autocrine stimulation and cell proliferation, which are responsible for the development of dermatofibrosarcoma protuberans. A reverse transcription-polymerase chain reaction assay was performed to detect the COL1A1-PDGFB fusion transcripts in 57 samples. In addition, the PDGFB gene amplification and PDGFB/PDGFRB mRNA levels were quantified by a real-time PCR system for the samples in which the fusion transcripts had been successfully detected. The fusion transcripts were detected in 42 of 57 samples. Various exons of the COL1A1 gene were fused in frame with the PDGFB gene; exons 7 and 25 were found to be slightly more frequently involved than the other exons. The PDGFB gene amplification levels varied from 0.6 to 8.3 (mean 2.4) in 42 tumor samples and from 0.4 to 3.0 (mean 1.2) in 20 adjacent normal tissue samples. In the 20 paired samples, the PDGFB gene amplification in the tumor was significantly higher than that in the normal tissue. The presence of PDGFB and PDGFRB mRNAs was demonstrated in 26 and 21 of 26 cases, respectively. The PDGFB and PDGFRB mRNA expression levels showed a good correlation (r ¼ 0.76, Po0.0001). These results indicate that the fusion protein, which is processed by the COL1A1-PDGFB transcripts, can serve as a functional ligand for PDGFRB. Keywords: dermatofibrosarcoma protuberans; COL1A1-PDGFB fusion transcripts; platelet-derived growth factor; platelet-derived growth factor receptor Dermatofibrosarcoma protuberans is a dermal and subcutaneous tumor of intermediate malignancy.Tumors are slow growing and rarely metastasize, but they are prone to local recurrence after surgery. Cytogenetic features of dermatofibrosarcoma protuberans include a recurrent translocation t(17;22, q22;q13) and supernumerary ring chromosomes. Translocation 17;22 has been shown to result in a fusion of the platelet-derived growth factor beta chain (PDGFB) gene in 22q13 with the collagen type I alpha 1 (COL1A1) gene in 17q22. In all analyzed translocations, the breakpoints occur in the intron preceding exon 2 of the PDGFB gene, whereas the COL1A1 part varies and includes various exons in the alpha-helical domain.1 The fusion deletes all known elements that negatively control PDGFB transcription and translation, which are considered as oncogene-activating events.2 The abnormal fusion transcripts probably cause PDGFB and its receptor (platelet-derived growth factor receptor beta, PDGFRB) autocrine stimulation and cell proliferation, which are responsible for the development of dermatofibrosarcoma protuberans. Recently, patients with unresectable dermatofibrosarcoma protuberans have been reported to be successfully

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“…[20][21][22][23] Regarding imatinib, a partial or fully favorable response can be noted in 50% of cases. 22,23 Another indication for TKIs in human medicine is preoperative treatment during 2 or 3 months as a means of facilitating surgical excision by reduction of adhesions, [21][22][23] also indicated in this case report.…”

mentioning

confidence: 99%

Medical approach to the treatment of feline injection site sarcoma with masitinib: a case report

Ledoux¹,

Brun²,

Chapuis³

et al. 2014

VMRR

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Feline injection site sarcoma is a common tumor among cats, for which existing medical treatments do not prove to be entirely satisfactory. In this tumor, the platelet-derived growth factor receptor, a tyrosine kinase receptor, is frequently hyperactivated. In the past, clinical case reports with imatinib, a tyrosine kinase inhibitor (TKI), have demonstrated tumoral stabilization. Here we describe the use of another TKI, masitinib, which specifically inhibits c-Kit, platelet-derived growth factor receptor, and Lyn, and is currently licensed for veterinary use in canine mast cell tumors. The therapeutic results were initially satisfactory, with regression of the tumor followed by tumoral recurrence which was stabilized and moderately reduced. Further studies are suggested, in order to evaluate the relevance of TKIs in the treatment and prevention of recurrences of feline injection site sarcoma. Tumoral stabilization by means of an inexpensive and reasonably well tolerated treatment would prove to be of true therapeutic relevance, in particular for inoperable feline injection site sarcomas. Another indication for such TKIs could be in preoperative treatment as a means of facilitating surgical excision by reduction of adhesions.

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Sustained complete remission of metastatic dermatofibrosarcoma protuberans with imatinib mesylate

Cited by 92 publications

References 5 publications

Gains of COL1A1-PDGFB genomic copies occur in fibrosarcomatous transformation of dermatofibrosarcoma protuberans

Gains of COL1A1-PDGFB genomic copies occur in fibrosarcomatous transformation of dermatofibrosarcoma protuberans

Detection of COL1A1-PDGFB fusion transcripts and PDGFB/PDGFRB mRNA expression in dermatofibrosarcoma protuberans

Medical approach to the treatment of feline injection site sarcoma with masitinib: a case report

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