ALK oncoproteins in atypical inflammatory myofibroblastic tumours: novel RRBP1-ALK fusions in epithelioid inflammatory myofibroblastic sarcoma

Jen Chieh Lee, Chien Feng Li, Hsuan Ying Huang, Mei Jun Zhu, Adrián Mariño-Enríquez, Chung Ta Lee, Wen Bin Ou, Jason L. Hornick, Jonathan A. Fletcher

研究成果: Article

22 引文 (Scopus)

摘要

ALK oncogenic activation mechanisms were characterized in four conventional spindle-cell inflammatory myofibroblastic tumours (IMT) and five atypical IMT, each of which had ALK genomic perturbations. Constitutively activated ALK oncoproteins were purified by ALK immunoprecipitation and electrophoresis, and were characterized by mass spectrometry. The four conventional IMT had TPM3/4-ALK fusions (two cases) or DCTN1-ALK fusions (two cases), whereas two atypical spindle-cell IMT had TFG-ALK and TPM3-ALK fusion in one case each, and three epithelioid inflammatory myofibroblastic sarcomas had RANBP2-ALK fusions in two cases, and a novel RRBP1-ALK fusion in one case. The epithelioid inflammatory myofibroblastic sarcoma with RRBP1-ALK fusion had cytoplasmic ALK expression with perinuclear accentuation, different from the nuclear membranous ALK localization in epithelioid inflammatory myofibroblastic sarcomas with RANBP2-ALK fusions. Evaluation of three additional uncharacterized epithelioid inflammatory myofibroblastic sarcomas with ALK cytoplasmic/perinuclear- accentuation expression demonstrated RRBP1-ALK fusion in two cases. These studies show that atypical spindle-cell IMT can utilize the same ALK fusion mechanisms described previously in conventional IMT, whereas in clinically aggressive epithelioid inflammatory myofibroblastic sarcoma we identify a novel recurrent ALK oncogenic mechanism, resulting from fusion with the RRBP1 gene.

原文English
頁(從 - 到)316-323
頁數8
期刊Journal of Pathology
241
發行號3
DOIs
出版狀態Published - 2017 二月 1

指紋

Oncogene Proteins
Sarcoma
Neoplasms
Immunoprecipitation
Electrophoresis
Mass Spectrometry
Genes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

引用此文

Lee, Jen Chieh ; Li, Chien Feng ; Huang, Hsuan Ying ; Zhu, Mei Jun ; Mariño-Enríquez, Adrián ; Lee, Chung Ta ; Ou, Wen Bin ; Hornick, Jason L. ; Fletcher, Jonathan A. / ALK oncoproteins in atypical inflammatory myofibroblastic tumours : novel RRBP1-ALK fusions in epithelioid inflammatory myofibroblastic sarcoma. 於: Journal of Pathology. 2017 ; 卷 241, 編號 3. 頁 316-323.
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title = "ALK oncoproteins in atypical inflammatory myofibroblastic tumours: novel RRBP1-ALK fusions in epithelioid inflammatory myofibroblastic sarcoma",
abstract = "ALK oncogenic activation mechanisms were characterized in four conventional spindle-cell inflammatory myofibroblastic tumours (IMT) and five atypical IMT, each of which had ALK genomic perturbations. Constitutively activated ALK oncoproteins were purified by ALK immunoprecipitation and electrophoresis, and were characterized by mass spectrometry. The four conventional IMT had TPM3/4-ALK fusions (two cases) or DCTN1-ALK fusions (two cases), whereas two atypical spindle-cell IMT had TFG-ALK and TPM3-ALK fusion in one case each, and three epithelioid inflammatory myofibroblastic sarcomas had RANBP2-ALK fusions in two cases, and a novel RRBP1-ALK fusion in one case. The epithelioid inflammatory myofibroblastic sarcoma with RRBP1-ALK fusion had cytoplasmic ALK expression with perinuclear accentuation, different from the nuclear membranous ALK localization in epithelioid inflammatory myofibroblastic sarcomas with RANBP2-ALK fusions. Evaluation of three additional uncharacterized epithelioid inflammatory myofibroblastic sarcomas with ALK cytoplasmic/perinuclear- accentuation expression demonstrated RRBP1-ALK fusion in two cases. These studies show that atypical spindle-cell IMT can utilize the same ALK fusion mechanisms described previously in conventional IMT, whereas in clinically aggressive epithelioid inflammatory myofibroblastic sarcoma we identify a novel recurrent ALK oncogenic mechanism, resulting from fusion with the RRBP1 gene.",
author = "Lee, {Jen Chieh} and Li, {Chien Feng} and Huang, {Hsuan Ying} and Zhu, {Mei Jun} and Adri{\'a}n Mari{\~n}o-Enr{\'i}quez and Lee, {Chung Ta} and Ou, {Wen Bin} and Hornick, {Jason L.} and Fletcher, {Jonathan A.}",
year = "2017",
month = "2",
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doi = "10.1002/path.4836",
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Lee, JC, Li, CF, Huang, HY, Zhu, MJ, Mariño-Enríquez, A, Lee, CT, Ou, WB, Hornick, JL & Fletcher, JA 2017, 'ALK oncoproteins in atypical inflammatory myofibroblastic tumours: novel RRBP1-ALK fusions in epithelioid inflammatory myofibroblastic sarcoma', Journal of Pathology, 卷 241, 編號 3, 頁 316-323. https://doi.org/10.1002/path.4836

ALK oncoproteins in atypical inflammatory myofibroblastic tumours : novel RRBP1-ALK fusions in epithelioid inflammatory myofibroblastic sarcoma. / Lee, Jen Chieh; Li, Chien Feng; Huang, Hsuan Ying; Zhu, Mei Jun; Mariño-Enríquez, Adrián; Lee, Chung Ta; Ou, Wen Bin; Hornick, Jason L.; Fletcher, Jonathan A.

於: Journal of Pathology, 卷 241, 編號 3, 01.02.2017, p. 316-323.

研究成果: Article

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T2 - novel RRBP1-ALK fusions in epithelioid inflammatory myofibroblastic sarcoma

AU - Lee, Jen Chieh

AU - Li, Chien Feng

AU - Huang, Hsuan Ying

AU - Zhu, Mei Jun

AU - Mariño-Enríquez, Adrián

AU - Lee, Chung Ta

AU - Ou, Wen Bin

AU - Hornick, Jason L.

AU - Fletcher, Jonathan A.

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N2 - ALK oncogenic activation mechanisms were characterized in four conventional spindle-cell inflammatory myofibroblastic tumours (IMT) and five atypical IMT, each of which had ALK genomic perturbations. Constitutively activated ALK oncoproteins were purified by ALK immunoprecipitation and electrophoresis, and were characterized by mass spectrometry. The four conventional IMT had TPM3/4-ALK fusions (two cases) or DCTN1-ALK fusions (two cases), whereas two atypical spindle-cell IMT had TFG-ALK and TPM3-ALK fusion in one case each, and three epithelioid inflammatory myofibroblastic sarcomas had RANBP2-ALK fusions in two cases, and a novel RRBP1-ALK fusion in one case. The epithelioid inflammatory myofibroblastic sarcoma with RRBP1-ALK fusion had cytoplasmic ALK expression with perinuclear accentuation, different from the nuclear membranous ALK localization in epithelioid inflammatory myofibroblastic sarcomas with RANBP2-ALK fusions. Evaluation of three additional uncharacterized epithelioid inflammatory myofibroblastic sarcomas with ALK cytoplasmic/perinuclear- accentuation expression demonstrated RRBP1-ALK fusion in two cases. These studies show that atypical spindle-cell IMT can utilize the same ALK fusion mechanisms described previously in conventional IMT, whereas in clinically aggressive epithelioid inflammatory myofibroblastic sarcoma we identify a novel recurrent ALK oncogenic mechanism, resulting from fusion with the RRBP1 gene.

AB - ALK oncogenic activation mechanisms were characterized in four conventional spindle-cell inflammatory myofibroblastic tumours (IMT) and five atypical IMT, each of which had ALK genomic perturbations. Constitutively activated ALK oncoproteins were purified by ALK immunoprecipitation and electrophoresis, and were characterized by mass spectrometry. The four conventional IMT had TPM3/4-ALK fusions (two cases) or DCTN1-ALK fusions (two cases), whereas two atypical spindle-cell IMT had TFG-ALK and TPM3-ALK fusion in one case each, and three epithelioid inflammatory myofibroblastic sarcomas had RANBP2-ALK fusions in two cases, and a novel RRBP1-ALK fusion in one case. The epithelioid inflammatory myofibroblastic sarcoma with RRBP1-ALK fusion had cytoplasmic ALK expression with perinuclear accentuation, different from the nuclear membranous ALK localization in epithelioid inflammatory myofibroblastic sarcomas with RANBP2-ALK fusions. Evaluation of three additional uncharacterized epithelioid inflammatory myofibroblastic sarcomas with ALK cytoplasmic/perinuclear- accentuation expression demonstrated RRBP1-ALK fusion in two cases. These studies show that atypical spindle-cell IMT can utilize the same ALK fusion mechanisms described previously in conventional IMT, whereas in clinically aggressive epithelioid inflammatory myofibroblastic sarcoma we identify a novel recurrent ALK oncogenic mechanism, resulting from fusion with the RRBP1 gene.

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