TET2 Mutations in Ph-Negative-Myeloproliferative Neoplasms: Identification of Three Novel Mutations and Relationship with Clinical and Laboratory Findings

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) were identified 2 mutations (8%); 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 patiens (n = 6) harboured TET2 mutations. Three unreported mutations were identified (p.P177fs, p.C1298del, 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 JAK2V617F-positive and -negative MPN and are more frequent in MPN-U patients. This could represent the biological link between the different classes of myeloid malignancies.