A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm

A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm

Abstract We describe a novel ERBB1/EGFR somatic mutation (p. C329R; c.985 T > C) identified in a patient with JAK2V617F Polycythaemia Vera (PV). This substitution affects a conserved cysteine residue in EGFR domain 2 and leads to the formation of a ligand-independent covalent receptor dimer, asso...

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Autores principales: D. A. Casolari, T. Nguyen, C. M. Butcher, D. G. Iarossi, C. N. Hahn, S. C. Bray, P. Neufing, W. T. Parker, J. Feng, K. Z. Y. Maung, A. Wee, L. Vidovic, C. H. Kok, P. G. Bardy, S. Branford, I. D. Lewis, S. W. Lane, H. S. Scott, D. M. Ross, R. J. D’Andrea
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/b3f3e98ac3f74378a5acf9fa8bc21d11
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spelling oai:doaj.org-article:b3f3e98ac3f74378a5acf9fa8bc21d112021-12-02T12:32:32ZA novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm10.1038/s41598-017-02655-72045-2322https://doaj.org/article/b3f3e98ac3f74378a5acf9fa8bc21d112017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02655-7https://doaj.org/toc/2045-2322Abstract We describe a novel ERBB1/EGFR somatic mutation (p. C329R; c.985 T > C) identified in a patient with JAK2V617F Polycythaemia Vera (PV). This substitution affects a conserved cysteine residue in EGFR domain 2 and leads to the formation of a ligand-independent covalent receptor dimer, associated with increased transforming potential. Aberrant signalling from the EGFRC329R receptor is cell type-dependent and in the TF1.8 erythroid cell line expression of this mutant suppresses EPO-induced differentiation. Clonal analysis shows that the dominant JAK2V617F-positive clone in this PV patient harbors EGFRC329R, thus this mutation may contribute to clonal expansion. Somatic mutations affecting other ERBB and related receptor tyrosine kinases are observed in myeloproliferative neoplasms (MPN), and we show elevated EGFR levels in MPN samples, consistent with previous reports. Thus activation of this group of receptors, via multiple mechanisms, may contribute to clonal growth and survival of the JAK2V617F disease clone in MPN.D. A. CasolariT. NguyenC. M. ButcherD. G. IarossiC. N. HahnS. C. BrayP. NeufingW. T. ParkerJ. FengK. Z. Y. MaungA. WeeL. VidovicC. H. KokP. G. BardyS. BranfordI. D. LewisS. W. LaneH. S. ScottD. M. RossR. J. D’AndreaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
D. A. Casolari
T. Nguyen
C. M. Butcher
D. G. Iarossi
C. N. Hahn
S. C. Bray
P. Neufing
W. T. Parker
J. Feng
K. Z. Y. Maung
A. Wee
L. Vidovic
C. H. Kok
P. G. Bardy
S. Branford
I. D. Lewis
S. W. Lane
H. S. Scott
D. M. Ross
R. J. D’Andrea
A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm
description Abstract We describe a novel ERBB1/EGFR somatic mutation (p. C329R; c.985 T > C) identified in a patient with JAK2V617F Polycythaemia Vera (PV). This substitution affects a conserved cysteine residue in EGFR domain 2 and leads to the formation of a ligand-independent covalent receptor dimer, associated with increased transforming potential. Aberrant signalling from the EGFRC329R receptor is cell type-dependent and in the TF1.8 erythroid cell line expression of this mutant suppresses EPO-induced differentiation. Clonal analysis shows that the dominant JAK2V617F-positive clone in this PV patient harbors EGFRC329R, thus this mutation may contribute to clonal expansion. Somatic mutations affecting other ERBB and related receptor tyrosine kinases are observed in myeloproliferative neoplasms (MPN), and we show elevated EGFR levels in MPN samples, consistent with previous reports. Thus activation of this group of receptors, via multiple mechanisms, may contribute to clonal growth and survival of the JAK2V617F disease clone in MPN.
format article
author D. A. Casolari
T. Nguyen
C. M. Butcher
D. G. Iarossi
C. N. Hahn
S. C. Bray
P. Neufing
W. T. Parker
J. Feng
K. Z. Y. Maung
A. Wee
L. Vidovic
C. H. Kok
P. G. Bardy
S. Branford
I. D. Lewis
S. W. Lane
H. S. Scott
D. M. Ross
R. J. D’Andrea
author_facet D. A. Casolari
T. Nguyen
C. M. Butcher
D. G. Iarossi
C. N. Hahn
S. C. Bray
P. Neufing
W. T. Parker
J. Feng
K. Z. Y. Maung
A. Wee
L. Vidovic
C. H. Kok
P. G. Bardy
S. Branford
I. D. Lewis
S. W. Lane
H. S. Scott
D. M. Ross
R. J. D’Andrea
author_sort D. A. Casolari
title A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm
title_short A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm
title_full A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm
title_fullStr A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm
title_full_unstemmed A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm
title_sort novel, somatic, transforming mutation in the extracellular domain of epidermal growth factor receptor identified in myeloproliferative neoplasm
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/b3f3e98ac3f74378a5acf9fa8bc21d11
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