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

D. A. Casolari, T. Nguyen, C. M. Butcher, D. G. Iarossi, Christopher N. Hahn, S. C. Bray, Petra J. Neufing, Wendy T. Parker, Jinghua Feng, K. Z.Y. Maung, A. Wee, Ljiljana Vidovic, C. H. Kok, P. G. Bardy, Susan Branford, Ian D. Lewis, S. W. Lane, Hamish S. Scott, David M. Ross, R. J. D'Andrea

Research output: Contribution to journalArticle

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.

LanguageEnglish
Article number2467
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

ASJC Scopus subject areas

  • General

Cite this

Casolari, D. A. ; Nguyen, T. ; Butcher, C. M. ; Iarossi, D. G. ; Hahn, Christopher N. ; Bray, S. C. ; Neufing, Petra J. ; Parker, Wendy T. ; Feng, Jinghua ; Maung, K. Z.Y. ; Wee, A. ; Vidovic, Ljiljana ; Kok, C. H. ; Bardy, P. G. ; Branford, Susan ; Lewis, Ian D. ; Lane, S. W. ; Scott, Hamish S. ; Ross, David M. ; D'Andrea, R. J. / A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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title = "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, 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.",
author = "Casolari, {D. A.} and T. Nguyen and Butcher, {C. M.} and Iarossi, {D. G.} and Hahn, {Christopher N.} and Bray, {S. C.} and Neufing, {Petra J.} and Parker, {Wendy T.} and Jinghua Feng and Maung, {K. Z.Y.} and A. Wee and Ljiljana Vidovic and Kok, {C. H.} and Bardy, {P. G.} and Susan Branford and Lewis, {Ian D.} and Lane, {S. W.} and Scott, {Hamish S.} and Ross, {David M.} and D'Andrea, {R. J.}",
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Casolari, DA, Nguyen, T, Butcher, CM, Iarossi, DG, Hahn, CN, Bray, SC, Neufing, PJ, Parker, WT, Feng, J, Maung, KZY, Wee, A, Vidovic, L, Kok, CH, Bardy, PG, Branford, S, Lewis, ID, Lane, SW, Scott, HS, Ross, DM & D'Andrea, RJ 2017, 'A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm', Scientific Reports, vol. 7, no. 1, 2467. https://doi.org/10.1038/s41598-017-02655-7

A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm. / Casolari, D. A.; Nguyen, T.; Butcher, C. M.; Iarossi, D. G.; Hahn, Christopher N.; Bray, S. C.; Neufing, Petra J.; Parker, Wendy T.; Feng, Jinghua; Maung, K. Z.Y.; Wee, A.; Vidovic, Ljiljana; Kok, C. H.; Bardy, P. G.; Branford, Susan; Lewis, Ian D.; Lane, S. W.; Scott, Hamish S.; Ross, David M.; D'Andrea, R. J.

In: Scientific Reports, Vol. 7, No. 1, 2467, 01.12.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm

AU - Casolari, D. A.

AU - Nguyen, T.

AU - Butcher, C. M.

AU - Iarossi, D. G.

AU - Hahn, Christopher N.

AU - Bray, S. C.

AU - Neufing, Petra J.

AU - Parker, Wendy T.

AU - Feng, Jinghua

AU - Maung, K. Z.Y.

AU - Wee, A.

AU - Vidovic, Ljiljana

AU - Kok, C. H.

AU - Bardy, P. G.

AU - Branford, Susan

AU - Lewis, Ian D.

AU - Lane, S. W.

AU - Scott, Hamish S.

AU - Ross, David M.

AU - D'Andrea, R. J.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41598-017-02655-7

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