title: Landscape of TET2 mutations in acute myeloid leukemia.
abstract: We investigated ten-eleven translocation 2 (TET2) mutations in acute myeloid leukemia (AML), their correlation with other gene mutations and prognostic value. By deep-sequencing, 131 somatic TET2 mutations were identified in 87/318 (27.4%) patients. Of 87 mutated cases, 44 (50.6%) carried two mutations. TET2 mutations were concomitantly observed with mutations in NPM1, FLT3-ITD, FLT3-TKD, JAK2, RUNX1, CEBPA, CBL and KRAS. However, TET2 mutations rarely concomitantly occurred with IDH1mut or IDH2mut (2/251 or 0/184; P=0.046 and P=0.003, respectively). TET2 mutations were associated with normal karyotype AML (CN-AML) (62/206 (30.1%) CN-AML vs 20/107 (18.7%) aberrant karyotype; P=0.031), higher white blood cell count (mean 65.3 vs 40.3 × 10(9)/l, P=0.023), lower platelet count (mean 68.6 vs 92.4 × 10(9)/l, P=0.03) and higher age (67.5 vs 65.2 years, P<0.001). Survival analyses were restricted to de novo CN-AML patients (n=165) and showed inferior event-free survival (EFS) of TET2 mutations compared with TET2wt (median: 6.7 vs 18.7 months, P=0.009). This negative effect of TET2 mutation on EFS was particularly observed in patients 65 years (median: 8.9 months vs not reached (n.r.), P=0.027) as well as in patients of the European LeukemiaNet favorable-risk subgroup, that is, patients harboring mutated CEBPA and/or mutated NPM1 without FLT3-ITD (median: 10.3 vs 41.3 months, P=0.048). These data support a role for TET2 as an important prognostic biomarker in AML.
authors: MLL Munich Leukemia Laboratory, Munich, Germany.
authors: S
authors: S
authors: Weissmann
authors: T
authors: T
authors: Alpermann
authors: V
authors: V
authors: Grossmann
authors: A
authors: A
authors: Kowarsch
authors: N
authors: N
authors: Nadarajah
authors: C
authors: C
authors: Eder
authors: F
authors: F
authors: Dicker
authors: A
authors: A
authors: Fasan
authors: C
authors: C
authors: Haferlach
authors: T
authors: T
authors: Haferlach
authors: W
authors: W
authors: Kern
authors: S
authors: S
authors: Schnittger
authors: A
authors: A
authors: Kohlmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002871:Chromosome Banding; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D000090243:Nucleophosmin; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C000716967:NPM1 protein, human; D011518:Proto-Oncogene Proteins; D000090243:Nucleophosmin; D049308:Dioxygenases; C541081:TET2 protein, human