Author(s)

Andrea Patriarca, Donatella Colaizzo, Gianluca Tiscia, Raffaele Spadano, Silvia Di Zacomo, Antonio Spadano, Ida Villanova, Maurizio Margaglione, Elvira Grandone, Alfredo Dragani

Atherosclerosis and Thrombosis Unit, IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy;.
Bleeding and Thrombotic Disorders Unit, Department of Hematology, Ospedale Civile Dello “Spirito Santo”, Pescara, Italy;.
Department of Medical Genetics, Foggia University, Foggia, Italy..
Laboratory of Molecular Biology, Department of Hematology, Ospedale Civile Dello “Spirito Santo”, Pescara, Italy;.

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.

MPN; Methylation; TET2; Molecular Biology

A. Patriarca, D. Colaizzo, G. Tiscia, R. Spadano, S. Zacomo, A. Spadano, I. Villanova, M. Margaglione, E. Grandone and A. Dragani, "TET2 Mutations in Ph-Negative-Myeloproliferative Neoplasms: Identification of Three Novel Mutations and Relationship with Clinical and Laboratory Findings," Open Journal of Blood Diseases, Vol. 3 No. 3, 2013, pp. 79-84. doi: 10.4236/ojbd.2013.33017.