TET2 mutations in B cells of patients affected by angioimmunoblastic T-cell lymphoma.
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.
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany.|Dr Senckenberg Institute of Pathology, Goethe-University of Frankfurt, Medical School, Frankfurt, Germany.
Friederike H
FH
Schwartz
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany.
Qian
Q
Cai
Dr Senckenberg Institute of Pathology, Goethe-University of Frankfurt, Medical School, Frankfurt, Germany.
Eva
E
Fellmann
Dr Senckenberg Institute of Pathology, Goethe-University of Frankfurt, Medical School, Frankfurt, Germany.
Sylvia
S
Hartmann
Department of Pathology, University of Helsinki, Helsinki, Finland.|HUSLAB, Division of Pathology, Meilahti Laboratories of Pathology, Helsinki University Central Hospital, Helsinki, Finland.
Mikko I
MI
Mäyränpää
Department of Pathology, University of Helsinki, Helsinki, Finland.|HUSLAB, Division of Pathology, Meilahti Laboratories of Pathology, Helsinki University Central Hospital, Helsinki, Finland.
Marja-Liisa
ML
Karjalainen-Lindsberg
Department of Immunology, Genetics and Pathology, Uppsala University Hospital, Uppsala, Sweden.
Christer
C
Sundström
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany.
René
R
Scholtysik
Dr Senckenberg Institute of Pathology, Goethe-University of Frankfurt, Medical School, Frankfurt, Germany.|German Cancer Consortium (DKTK), Germany.
Martin-Leo
ML
Hansmann
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany.|German Cancer Consortium (DKTK), Germany.
Ralf
0000-0002-6691-7191
R
Küppers
D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D005260:Female; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000235:genetics*; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D061346:Laser Capture Microdissection; D008198:Lymph Nodes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; D049308:Dioxygenases; C541081:TET2 protein, human
B cells; IDH2; TET2; angioimmunoblastic T-cell lymphoma; somatic mutation