title: TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis.
abstract: 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 approximately 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 approximately 16, 5, 17, 14, 14 and 17% (P=0.50). Mutant TET2 was detected in approximately 17 and approximately 7% of JAK2V617F-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 approximately 23% in patients > or =60 years old versus approximately 4% in younger patients (P<0.0001). The presence of mutant TET2 did not affect survival, leukemic transformation or thrombosis in either PV or PMF; a correlation with hemoglobin <10 g per 100 ml in PMF was noted (P=0.05). We conclude that TET2 mutations occur in both JAK2V617F-positive and -negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance.
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA. tefferi.ayalew@mayo.edu
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
authors.forename: A
authors.initials: A
authors.lastname: Pardanani
authors.forename: K-H
authors.initials: KH
authors.lastname: Lim
authors.forename: O
authors.initials: O
authors.lastname: Abdel-Wahab
authors.forename: T L
authors.initials: TL
authors.lastname: Lasho
authors.forename: J
authors.initials: J
authors.lastname: Patel
authors.forename: N
authors.initials: N
authors.lastname: Gangat
authors.forename: C M
authors.initials: CM
authors.lastname: Finke
authors.forename: S
authors.initials: S
authors.lastname: Schwager
authors.forename: A
authors.initials: A
authors.lastname: Mullally
authors.forename: C-Y
authors.initials: CY
authors.lastname: Li
authors.forename: C A
authors.initials: CA
authors.lastname: Hanson
authors.forename: R
authors.initials: R
authors.lastname: Mesa
authors.forename: O
authors.initials: O
authors.lastname: Bernard
authors.forename: F
authors.initials: F
authors.lastname: Delhommeau
authors.forename: W
authors.initials: W
authors.lastname: Vainchenker
authors.forename: D G
authors.initials: DG
authors.lastname: Gilliland
authors.forename: R L
authors.initials: RL
authors.lastname: Levine
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011087:Polycythemia Vera / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015996:Survival Rate; D013920:Thrombocythemia, Essential / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2