TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis

High-throughput DNA sequence analysis was used to screen for TET2 mutations in bone marrow-derived DNA from 239 patients with BCR-ABL -negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of ∼13%. Specific diagnoses included polycythemia vera (PV; n =89), essential thrombocythemia (ET; n =57), primary myelofibrosis (PMF; n =60), post-PV MF ( n =14), post-ET MF ( n =7) and blast phase PV/ET/MF ( n =12); the corresponding mutational frequencies were ∼16, 5, 17, 14, 14 and 17% ( P =0.50). Mutant TET2 was detected in ∼17 and ∼7% of JAK2 V617F-positive and -negative cases, respectively ( P =0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant TET2 and advanced age; mutational frequency was ∼23% in patients ⩾60 years old versus ∼4% in younger patients ( P