title: TET2 mutations in Ph-negative myeloproliferative neoplasms: identification of three novel mutations and relationship with clinical and laboratory findings.
abstract: High-throughput DNA sequence analysis was used to screen for TET2 mutations in peripheral blood derived DNA from 97 patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). Overall six mutations in the coding region of the gene were identified in 7 patients with an overall mutational frequency of 7.2%. In polycythemia vera patients (n = 25) 2 mutations were identified (8%), and in those with essential thrombocythemia (n = 55) 2 mutations (3.6%); in those with unclassifiable MPN (n = 8) 3 mutations (37.5%). No primary myelofibrosis patients (n = 6) harboured TET2 mutations. Three unreported mutations were identified (p.P177fs, p.C1298del, and p.P411del), the first two in patients with unclassifiable MPN, the last in a patient with essential thrombocythemia. On multivariate analysis the diagnosis of an unclassifiable MPN was significantly related to the presence of TET2 mutations (P = 0.02; OR: 2.81; 95% CI 1.11-7.06). We conclude that TET2 mutations occur in both JAK2 V617F-positive and -negative MPNs and are more frequent in MPN-U patients. This could represent the biological link between the different classes of myeloid malignancies.
authors.affiliation: Bleeding and Thrombotic Disorders Unit, Department of Hematology, Ospedale Civile dello Spirito Santo, 65124 Pescara, Italy. andreapatriarca80@gmail.com
authors.forename: Andrea
authors.initials: A
authors.lastname: Patriarca
authors.forename: Donatella
authors.initials: D
authors.lastname: Colaizzo
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tiscia
authors.forename: Raffaele
authors.initials: R
authors.lastname: Spadano
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Zacomo
authors.forename: Antonio
authors.initials: A
authors.lastname: Spadano
authors.forename: Ida
authors.initials: I
authors.lastname: Villanova
authors.forename: Maurizio
authors.initials: M
authors.lastname: Margaglione
authors.forename: Elvira
authors.initials: E
authors.lastname: Grandone
authors.forename: Alfredo
authors.initials: A
authors.lastname: Dragani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D010677:Philadelphia Chromosome; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013927:Thrombosis / Q000150:complications / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human