title: Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disorders.
abstract: We searched for JAK2 exon 12 mutations in patients with JAK2 (V617F)-negative myeloproliferative disorders. Seventeen patients with polycythemia vera (PV), including 15 sporadic cases and 2 familial cases, carried deletions or duplications of exon 12 in circulating granulocytes but not in T lymphocytes. Two of the 8 mutations detected were novel, and the most frequent ones were N542-E543del and E543-D544del. Most patients with PV carrying an exon 12 mutation had isolated erythrocytosis at clinical onset, unlike patients with JAK2 (V617F)-positive PV, most of whom had also elevations in white blood cell and/or platelet counts. Both patients with familial PV carrying an exon 12 mutation had an affected sibling with JAK2 (V617F)-positive PV. Thus, several somatic mutations of JAK2 exon 12 can be found in a myeloproliferative disorder that is mainly characterized by erythrocytosis. Moreover, a genetic predisposition to acquisition of different JAK2 mutations is inherited in families with myeloproliferative disorders.
authors.affiliation: Department of Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo and University of Pavia, Pavia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pietra
authors.forename: Sai
authors.initials: S
authors.lastname: Li
authors.forename: Angela
authors.initials: A
authors.lastname: Brisci
authors.forename: Francesco
authors.initials: F
authors.lastname: Passamonti
authors.forename: Elisa
authors.initials: E
authors.lastname: Rumi
authors.forename: Alexandre
authors.initials: A
authors.lastname: Theocharides
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ferrari
authors.forename: Heinz
authors.initials: H
authors.lastname: Gisslinger
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
authors.forename: Laura
authors.initials: L
authors.lastname: Cremonesi
authors.forename: Radek
authors.initials: R
authors.lastname: Skoda
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000201:enzymology* / Q000235:genetics*; D010375:Pedigree; D014633:Valine / Q000235:genetics / Q000378:metabolism
chemical_list: D053614:Janus Kinase 2; D014633:Valine