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TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele
Author(s) -
Bacher Ulrike,
Weissmann Sandra,
Kohlmann Alexander,
Schindela Sonja,
Alpermann Tamara,
Schnittger Susanne,
Kern Wolfgang,
Haferlach Torsten,
Haferlach Claudia
Publication year - 2012
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2011.08911.x
Subject(s) - myeloid , biology , myelodysplastic syndromes , cytogenetics , cancer research , myeloid leukemia , microbiology and biotechnology , genetics , bone marrow , immunology , gene , chromosome
Summary TET2 mutations have been identified in 10–25% of patients with myeloid malignancies, but TET2 gene copy number alterations remain to be evaluated. We performed interphase and metaphase fluorescence in situ hybridization (FISH), using newly designed probes that span TET2, in 893 patients with acute myeloid leukaemia (AML) and chronic myeloid malignancies and validated the new assay by single nucleotide polymorphism arrays. Next‐generation sequencing for molecular TET2 mutations was performed in 37/50 del( TET2 ) patients. We identified TET2 deletions in 50/893 patients (26 males, 24 females; 44–87 years) resulting in a 5·6% frequency [22/425 AML (5·2%), 15/217 chronic myelomonocytic leukaemia (CMML; 6·9%), 9/188 myelodysplastic syndromes (4·8%), 4/63 myeloproliferative neoplasms (6·3%)]. Cytogenetic alterations (mostly complex) were detected in 35/50 (70·0%) of del( TET2 ) cases. TET2 deletions were cytogenetically cryptic in 25/50 (50·0%). Sequencing detected TET2 mut in 19/37 (51·4%) del( TET2 ) cases investigated, predominantly CMML (10/14; 71·4%). In de novo AML with intermediate cytogenetics, presence of any TET2 alteration was related to worse median overall survival (347 d vs. not reached; P = 0·052) and event‐free survival (164 vs. 457 d; P = 0·024). JAK2 V617F was found in 6/18 (33·3%) del( TET2 ) cases analysed. Thus, TET2 haploinsufficiency recurrently occurs in myeloid malignancies, frequently combined with TET2 mutations on the remaining allele. The prognostic impact of del( TET2 ) in myeloid malignancies should be further evaluated.