Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib target exploration consortium study B2225

Grant A. McArthur, George D. Demetri, Allan Van Oosterom, Michael Heinrich, Maria Debiec-Rychter, Christopher Corless, Zariana Nikolova, Sasa Dimitrijevic, Jonathan A. Fletcher

Research output: Contribution to journalArticle

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Abstract

Purpose: The cutaneous malignant tumor dermatofibrosarcoma protuberans (DFSP) is typically associated with a translocation between chromosomes 17 and 22 that places the platelet-derived growth factor-B (PDGFB) under the control of the collagen 1A1 promoter. The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib. Patients and Methods: We analyzed the objective radiologic and clinical response to imatinib at 400 mg twice daily in eight patients with locally advanced DFSP and two patients with metastatic disease. Results: Each of eight patients with locally advanced DFSP had evidence of t(17;22) and showed a clinical response to imatinib. Four of these patients had complete clinical responses. The two patients with metastatic disease had fibrosarcomatous histology and karyotypes that were substantially more complex than those typically associated with localized DFSP. One patient with metastatic DFSP and an associated t(17;22) had a partial response to imatinib but experienced disease progression after 7 months of therapy. In contrast, the other patient with metastatic disease had a tumor lacking t(17;22), and there was no clinical response to imatinib. Unexpectedly, there was minimal platelet-derived growth factor receptor-beta phosphorylation in the untreated DFSP, despite the documented presence of a PDGFB autocrine mechanism. Conclusion: Imatinib has clinical activity against both localized and metastatic DFSP with t(17;22). However, fibrosarcomatous variants of DFSP lacking t(17;22) may not respond to imatinib.

Original languageEnglish (US)
Pages (from-to)866-873
Number of pages8
JournalJournal of Clinical Oncology
Volume23
Issue number4
DOIs
StatePublished - 2005
Externally publishedYes

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Dermatofibrosarcoma
Proto-Oncogene Proteins c-sis
Platelet-Derived Growth Factor beta Receptor
Imatinib Mesylate
Chromosomes, Human, Pair 22
Chromosomes, Human, Pair 17
Karyotype
Cytogenetics
Disease Progression
Neoplasms
Histology
Phosphotransferases
Collagen
Phosphorylation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib : Imatinib target exploration consortium study B2225. / McArthur, Grant A.; Demetri, George D.; Van Oosterom, Allan; Heinrich, Michael; Debiec-Rychter, Maria; Corless, Christopher; Nikolova, Zariana; Dimitrijevic, Sasa; Fletcher, Jonathan A.

In: Journal of Clinical Oncology, Vol. 23, No. 4, 2005, p. 866-873.

Research output: Contribution to journalArticle

McArthur, Grant A. ; Demetri, George D. ; Van Oosterom, Allan ; Heinrich, Michael ; Debiec-Rychter, Maria ; Corless, Christopher ; Nikolova, Zariana ; Dimitrijevic, Sasa ; Fletcher, Jonathan A. / Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib : Imatinib target exploration consortium study B2225. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 4. pp. 866-873.
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abstract = "Purpose: The cutaneous malignant tumor dermatofibrosarcoma protuberans (DFSP) is typically associated with a translocation between chromosomes 17 and 22 that places the platelet-derived growth factor-B (PDGFB) under the control of the collagen 1A1 promoter. The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib. Patients and Methods: We analyzed the objective radiologic and clinical response to imatinib at 400 mg twice daily in eight patients with locally advanced DFSP and two patients with metastatic disease. Results: Each of eight patients with locally advanced DFSP had evidence of t(17;22) and showed a clinical response to imatinib. Four of these patients had complete clinical responses. The two patients with metastatic disease had fibrosarcomatous histology and karyotypes that were substantially more complex than those typically associated with localized DFSP. One patient with metastatic DFSP and an associated t(17;22) had a partial response to imatinib but experienced disease progression after 7 months of therapy. In contrast, the other patient with metastatic disease had a tumor lacking t(17;22), and there was no clinical response to imatinib. Unexpectedly, there was minimal platelet-derived growth factor receptor-beta phosphorylation in the untreated DFSP, despite the documented presence of a PDGFB autocrine mechanism. Conclusion: Imatinib has clinical activity against both localized and metastatic DFSP with t(17;22). However, fibrosarcomatous variants of DFSP lacking t(17;22) may not respond to imatinib.",
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T1 - Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib

T2 - Imatinib target exploration consortium study B2225

AU - McArthur, Grant A.

AU - Demetri, George D.

AU - Van Oosterom, Allan

AU - Heinrich, Michael

AU - Debiec-Rychter, Maria

AU - Corless, Christopher

AU - Nikolova, Zariana

AU - Dimitrijevic, Sasa

AU - Fletcher, Jonathan A.

PY - 2005

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N2 - Purpose: The cutaneous malignant tumor dermatofibrosarcoma protuberans (DFSP) is typically associated with a translocation between chromosomes 17 and 22 that places the platelet-derived growth factor-B (PDGFB) under the control of the collagen 1A1 promoter. The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib. Patients and Methods: We analyzed the objective radiologic and clinical response to imatinib at 400 mg twice daily in eight patients with locally advanced DFSP and two patients with metastatic disease. Results: Each of eight patients with locally advanced DFSP had evidence of t(17;22) and showed a clinical response to imatinib. Four of these patients had complete clinical responses. The two patients with metastatic disease had fibrosarcomatous histology and karyotypes that were substantially more complex than those typically associated with localized DFSP. One patient with metastatic DFSP and an associated t(17;22) had a partial response to imatinib but experienced disease progression after 7 months of therapy. In contrast, the other patient with metastatic disease had a tumor lacking t(17;22), and there was no clinical response to imatinib. Unexpectedly, there was minimal platelet-derived growth factor receptor-beta phosphorylation in the untreated DFSP, despite the documented presence of a PDGFB autocrine mechanism. Conclusion: Imatinib has clinical activity against both localized and metastatic DFSP with t(17;22). However, fibrosarcomatous variants of DFSP lacking t(17;22) may not respond to imatinib.

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