TET2 mutations in B cells of patients affected by angioimmunoblastic T‐cell lymphoma |
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Authors: | Eva Fellmann Sylvia Hartmann Mikko I Mäyränpää Marja‐Liisa Karjalainen‐Lindsberg Christer Sundström Ralf Küppers |
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Affiliation: | 1. Dr Senckenberg Institute of Pathology, Goethe‐University of Frankfurt, Medical School, Frankfurt, Germany;2. Department of Pathology, University of Helsinki, Helsinki, Finland;3. HUSLAB, Division of Pathology, Meilahti Laboratories of Pathology, Helsinki University Central Hospital, Helsinki, Finland;4. Department of Immunology, Genetics and Pathology, Uppsala University Hospital, Uppsala, Sweden;5. Institute of Cell Biology (Cancer Research), University of Duisburg‐Essen, Medical School, Essen, Germany;6. German Cancer Consortium (DKTK), GermanyCo‐senior authors. |
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Abstract: | Angioimmunoblastic T‐cell lymphomas (AITLs) frequently carry mutations in the TET2 and IDH2 genes. TET2 mutations represent early genetic lesions as they had already been detected in haematopoietic precursor cells of AITL patients. We show by analysis of whole‐tissue sections and microdissected PD1+ cells that the frequency of TET2‐mutated AITL is presumably even higher than reported (12/13 cases in our collection; 92%). In two‐thirds of informative AITLs (6/9), a fraction of B cells was also TET2‐mutated. Investigation of four AITLs by TET2 and IGHV gene sequencing of single microdissected B cells showed that between 10% and 60% of polyclonal B cells in AITL lymph nodes harboured the identical TET2 mutations of the respective T‐cell lymphoma clone. Thus, TET2‐mutated haematopoietic precursor cells in AITL patients not only give rise to the T‐cell lymphoma but also generate a large population of mutated mature B cells. Future studies will show whether this is a reason why AITL patients frequently also develop B‐cell lymphomas. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
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Keywords: | angioimmunoblastic T‐cell lymphoma B cells IDH2 somatic mutation TET2 |
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