TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele.
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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. / Bacher, Ulrike; Weissmann, Sandra; Kohlmann, Alexander; Schindela, Sonja; Alpermann, Tamara; Schnittger, Susanne; Kern, Wolfgang; Haferlach, Torsten; Haferlach, Claudia.
in: BRIT J HAEMATOL, Jahrgang 156, Nr. 1, 1, 2012, S. 67-75.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele.
AU - Bacher, Ulrike
AU - Weissmann, Sandra
AU - Kohlmann, Alexander
AU - Schindela, Sonja
AU - Alpermann, Tamara
AU - Schnittger, Susanne
AU - Kern, Wolfgang
AU - Haferlach, Torsten
AU - Haferlach, Claudia
PY - 2012
Y1 - 2012
N2 - 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 TET2mut 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.
AB - 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 TET2mut 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.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Prognosis
KW - Gene Expression Regulation
KW - Gene Deletion
KW - Gene Frequency
KW - Gene Expression Profiling
KW - Kaplan-Meier Estimate
KW - Alleles
KW - DNA-Binding Proteins/genetics
KW - Haploinsufficiency
KW - Karyotyping
KW - Leukemia, Myeloid/diagnosis/genetics/mortality
KW - Mutation
KW - Myelodysplastic Syndromes/diagnosis/genetics/mortality
KW - Myeloproliferative Disorders/diagnosis/genetics/mortality
KW - Proto-Oncogene Proteins/genetics
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Prognosis
KW - Gene Expression Regulation
KW - Gene Deletion
KW - Gene Frequency
KW - Gene Expression Profiling
KW - Kaplan-Meier Estimate
KW - Alleles
KW - DNA-Binding Proteins/genetics
KW - Haploinsufficiency
KW - Karyotyping
KW - Leukemia, Myeloid/diagnosis/genetics/mortality
KW - Mutation
KW - Myelodysplastic Syndromes/diagnosis/genetics/mortality
KW - Myeloproliferative Disorders/diagnosis/genetics/mortality
KW - Proto-Oncogene Proteins/genetics
M3 - SCORING: Journal article
VL - 156
SP - 67
EP - 75
JO - BRIT J HAEMATOL
JF - BRIT J HAEMATOL
SN - 0007-1048
IS - 1
M1 - 1
ER -