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

Abstract EN

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.