Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/110830
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Type: Journal article
Title: A novel, somatic, transforming mutation in the extracellular domain of epidermal growth factor receptor identified in myeloproliferative neoplasm
Author: Casolari, D.
Nguyen, T.
Butcher, C.
Iarossi, D.
Hahn, C.
Bray, S.
Neufing, P.
Parker, W.
Feng, J.
Maung, K.
Wee, A.
Vidovic, L.
Kok, C.
Bardy, P.
Branford, S.
Lewis, I.
Lane, S.
Scott, H.
Ross, D.
D'Andrea, R.
Citation: Scientific Reports, 2017; 7(1):2467-1-2467-9
Publisher: Springer Nature
Issue Date: 2017
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
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
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.
Keywords: Myeloproliferative disease; oncogenes
Rights: © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
RMID: 0030070425
DOI: 10.1038/s41598-017-02655-7
Grant ID: http://purl.org/au-research/grants/nhmrc/1063443
Appears in Collections:Molecular and Biomedical Science publications

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