TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele.

Ulrike Bacher; Sandra Weissmann; Alexander Kohlmann; Sonja Schindela; Tamara Alpermann; Susanne Schnittger; Wolfgang Kern; Torsten Haferlach; Claudia Haferlach

TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele.

Standard

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, Vol. 156, No. 1, 1, 2012, p. 67-75.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Bacher, U, Weissmann, S, Kohlmann, A, Schindela, S, Alpermann, T, Schnittger, S, Kern, W, Haferlach, T & Haferlach, C 2012, 'TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele.', BRIT J HAEMATOL, vol. 156, no. 1, 1, pp. 67-75. <http://www.ncbi.nlm.nih.gov/pubmed/22017486?dopt=Citation>

APA

Bacher, U., Weissmann, S., Kohlmann, A., Schindela, S., Alpermann, T., Schnittger, S., Kern, W., Haferlach, T., & Haferlach, C. (2012). TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele. BRIT J HAEMATOL, 156(1), 67-75. [1]. http://www.ncbi.nlm.nih.gov/pubmed/22017486?dopt=Citation

Vancouver

Bacher U, Weissmann S, Kohlmann A, Schindela S, Alpermann T, Schnittger S et al. TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele. BRIT J HAEMATOL. 2012;156(1):67-75. 1.

Bibtex

@article{9507ad3ba4d1404f9f506de515de1cbc,

title = "TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele.",

abstract = "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.",

keywords = "Adult, Humans, Male, Aged, Female, Middle Aged, Aged, 80 and over, Prognosis, Gene Expression Regulation, Gene Deletion, Gene Frequency, Gene Expression Profiling, Kaplan-Meier Estimate, *Alleles, DNA-Binding Proteins/*genetics, Haploinsufficiency, Karyotyping, Leukemia, Myeloid/diagnosis/*genetics/mortality, *Mutation, Myelodysplastic Syndromes/diagnosis/*genetics/mortality, Myeloproliferative Disorders/diagnosis/*genetics/mortality, Proto-Oncogene Proteins/*genetics, Adult, Humans, Male, Aged, Female, Middle Aged, Aged, 80 and over, Prognosis, Gene Expression Regulation, Gene Deletion, Gene Frequency, Gene Expression Profiling, Kaplan-Meier Estimate, *Alleles, DNA-Binding Proteins/*genetics, Haploinsufficiency, Karyotyping, Leukemia, Myeloid/diagnosis/*genetics/mortality, *Mutation, Myelodysplastic Syndromes/diagnosis/*genetics/mortality, Myeloproliferative Disorders/diagnosis/*genetics/mortality, Proto-Oncogene Proteins/*genetics",

author = "Ulrike Bacher and Sandra Weissmann and Alexander Kohlmann and Sonja Schindela and Tamara Alpermann and Susanne Schnittger and Wolfgang Kern and Torsten Haferlach and Claudia Haferlach",

year = "2012",

language = "English",

volume = "156",

pages = "67--75",

journal = "BRIT J HAEMATOL",

issn = "0007-1048",

publisher = "Wiley-Blackwell",

number = "1",

}

RIS

TY - JOUR

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 -