title: Isotype-switched follicular lymphoma displays dissociation between activation-induced cytidine deaminase expression and somatic hypermutation.
abstract: In B-cells, activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. AID introduces mutations in immunoglobulin variable regions (IGV) during B-cell receptor affinity maturation, but may also introduce aberrant mutations into non-immunoglobulin genes, most commonly BCL6. Follicular lymphoma (FL) B-cells constitutively express AID and undergo CSR, SHM and aberrant SHM. We have studied AID expression, the presence of SHM mutations, CSR, and aberrant SHM in BCL6 in a cohort of 75 FL patients. Whereas IgM-expressing (non-switched) FL were characterized by an expected positive correlation between AID and IGV and BCL6 mutations, isotype-switched FL showed dissociation between AID expression and aberrant SHM, and inverse correlation between SHM and AID expression. Our results unveil two manifest biological subgroups of FL and indicate that the specific dissociation between AID and SHM after isotype switch may correlate with the clinical outcome of this heterogeneous disease.
authors: a Department of Hematology and Oncology , University Medical Center Freiburg , Germany.
authors: Florian
authors: F
authors: Scherer
authors: b Department of Hematology , Leiden University Medical Center , The Netherlands.|c School of Medicine, University of Magallanes , Punta Arenas , Chile.
authors: Marcelo A
authors: MA
authors: Navarrete
authors: a Department of Hematology and Oncology , University Medical Center Freiburg , Germany.
authors: Cristina
authors: C
authors: Bertinetti-Lapatki
authors: d Department of Pathology , RWTH University Hospital , Aachen , Germany.
authors: Joachim
authors: J
authors: Boehm
authors: e Department of Pathology , University Medical Center Freiburg , Germany.
authors: Annette
authors: A
authors: Schmitt-Graeff
authors: b Department of Hematology , Leiden University Medical Center , The Netherlands.
authors: Hendrik
authors: H
authors: Veelken
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D003564:Cytidine Deaminase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D051560:Proto-Oncogene Proteins c-bcl-6; D027041:Somatic Hypermutation, Immunoglobulin; D015533:Transcriptional Activation; D055815:Young Adult
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051560:Proto-Oncogene Proteins c-bcl-6; D003564:Cytidine Deaminase
keywords: Aberrant somatic hypermutation; B-cell receptor; activation-induced cytidine deaminase; follicular lymphoma; somatic hypermutation