title: CALR mutation profile in Irish patients with myeloproliferative neoplasms.
abstract: Insertion and/or deletion mutations of the CALR gene have recently been demonstrated to be the second most common driver mutations in the myeloproliferative neoplasms (MPNs) of essential thrombocythemia (ET) and primary myelofibrosis (PMF). Given the diagnostic and emerging prognostic significance of these mutations, in addition to the geographical heterogeneity reported, the incidence of CALR mutations was determined in an Irish cohort of patients with MPNs with a view to incorporate this analysis into a prospective screening program. A series of 202 patients with known or suspected ET and PMF were screened for the presence of CALR mutations. CALR mutations were detected in 58 patients. Type 1 and Type 1-like deletion mutations were the most common (n=40) followed by Type 2 and Type 2-like insertion mutations (n=17). The CALR mutation profile in Irish ET and PMF patients appears similar to that in other European populations. Establishment of this mutational profile allows the introduction of a rational, molecular diagnostic algorithm in cases of suspected ET and PMF that will improve clinical management.
authors.affiliation: Cancer Molecular Diagnostics, St. James's Hospital, Dublin, Ireland.
authors.forename: Karl
authors.initials: K
authors.lastname: Haslam
authors.affiliation: Department of Haematology, St. James's Hospital, Dublin, Ireland.
authors.forename: Eibhlin
authors.initials: E
authors.lastname: Conneally
authors.affiliation: Department of Haematology, St. James's Hospital, Dublin, Ireland.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Flynn
authors.affiliation: Department of Haematology, Cork University Hospital, Cork, Ireland.
authors.forename: Mary R
authors.initials: MR
authors.lastname: Cahill
authors.affiliation: Department of Haematology, Cork University Hospital, Cork, Ireland.
authors.forename: Oonagh
authors.initials: O
authors.lastname: Gilligan
authors.affiliation: Department of Haematology, Cork University Hospital, Cork, Ireland.
authors.forename: Derville
authors.initials: D
authors.lastname: O'Shea
authors.affiliation: Cancer Molecular Diagnostics, St. James's Hospital, Dublin, Ireland. Electronic address: slangabeer@stjames.ie.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Langabeer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019046:Bone Marrow Neoplasms / Q000235:genetics*; D037282:Calreticulin / Q000235:genetics*; D005260:Female; D006801:Humans; D007494:Ireland; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics*
chemical_list: D037282:Calreticulin
keywords: CALR; Essential thrombocythemia; JAK2; Myeloproliferative neoplasm; Primary myelofibrosis