Journal article

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

DA Casolari, T Nguyen, CM Butcher, DG Iarossi, CN Hahn, SC Bray, P Neufing, WT Parker, J Feng, KZY Maung, A Wee, L Vidovic, CH Kok, PG Bardy, S Branford, ID Lewis, SW Lane, HS Scott, DM Ross, RJ D'Andrea



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 ..

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Awarded by National Health & Medical Research Council of Australia

Funding Acknowledgements

We thank all patients who gave samples for this study, and the South Australian Cancer Research Biobank (SACRB) for their assistance with sample collection and storage. This research was funded by the National Health & Medical Research Council of Australia (Project Grant #1063443).