B-Lymphoblastic Lymphomas Evolving from Follicular Lymphomas Co-Express Surrogate Light Chains and Mutated Gamma Heavy Chains
Autor: | Bart J. Biemond, Philippus Kluin, Thera A. M. Wormhoudt, Andre B. Mulder, Monique E.C.M. Oud, Linda M. Slot, Robbert Hoogeboom, Aldo Jongejan, Laura A. Smit, Richard J. Bende, Antoine H. C. van Kampen, Carel J. M. van Noesel, Esther J. M. Schilder-Tol, Jeroen E. J. Guikema |
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Přispěvatelé: | Graduate School, Other departments, CCA -Cancer Center Amsterdam, Pathology, AII - Amsterdam institute for Infection and Immunity, Clinical Haematology, Epidemiology and Data Science, APH - Amsterdam Public Health, Biosystems Data Analysis (SILS, FNWI), Stem Cell Aging Leukemia and Lymphoma (SALL) |
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine DNA Mutational Analysis Follicular lymphoma GENE ANALYSIS MOLECULAR ANALYSIS medicine.disease_cause Translocation Genetic Loss of heterozygosity 0302 clinical medicine Cyclin D3 Lymphoma Follicular In Situ Hybridization Fluorescence B-Lymphocytes Comparative Genomic Hybridization Mutation Neurofibromin 1 medicine.diagnostic_test DNA COPY NUMBER Middle Aged 030220 oncology & carcinogenesis Female IGHV@ Receptors Tumor Necrosis Factor Member 14 Lymphoma B-Cell Immunoglobulin Light Chains Surrogate CELL LYMPHOMAS Immunoglobulin gamma-Chains Nonsense mutation Biology Immunoglobulin light chain Pathology and Forensic Medicine Young Adult 03 medical and health sciences medicine C-MYC Cyclin-Dependent Kinase Inhibitor p18 Humans NON-HODGKINS-LYMPHOMA Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor p15 Germinal Center medicine.disease Molecular biology TRANSFORMATION Lymphoma 030104 developmental biology IMMUNOGLOBULIN LEUKEMIA Transcription Factors Fluorescence in situ hybridization CLASS SWITCH RECOMBINATION |
Zdroj: | American journal of pathology, 186(12), 3273-3284. Elsevier Inc. Slot, L M, Hoogeboom, R, Smit, L A, Wormhoudt, T A M, Biemond, B J, Oud, M E C M, Schilder-Tol, E J M, Mulder, A B, Jongejan, A, van Kampen, A H C, Kluin, P M, Guikema, J E J, Bende, R J & van Noesel, C J M 2016, ' B-Lymphoblastic Lymphomas Evolving from Follicular Lymphomas Co-Express Surrogate Light Chains and Mutated Gamma Heavy Chains ', American Journal of Pathology, vol. 186, no. 12, pp. 3273-3284 . https://doi.org/10.1016/j.ajpath.2016.07.027 The American Journal of Pathology, 186(12), 3273-3284. Elsevier The American Journal of Pathology, 186(12), 3273-3284. ELSEVIER SCIENCE INC |
ISSN: | 0002-9440 |
DOI: | 10.1016/j.ajpath.2016.07.027 |
Popis: | Follicular lymphoma (FL) is an indolent B-cell non-Hodgkin lymphoma able to transform into germinal center-type diffuse large B-cell lymphoma. We describe four extraordinary cases of FL, which progressed to TdT+CD20- precursor B-lymphoblastic lymphoma (B-LBL). Fluorescence in situ hybridization analysis showed that all four B-LBLs had acquired a MYC translocation on transformation. Comparative genomic hybridization analysis of one case demonstrated that in addition to 26 numerical aberrations that were shared between the FL and B-LBL, deletion of CDKN2A/B and 17q11, 14q32 amplification, and copy-neutral loss of heterozygosity of 9p were gained in the B-LBL cells. Whole-exome sequencing revealed mutations in FMN2, NEB, and SYNE1 and a nonsense mutation in KMT2D, all shared by the FL and B-LBL, and TNFRSF14, SMARCA2, CCND3 mutations uniquely present in the B-LBL. Remarkably, all four FL-B-LBL pairs expressed IgG. In two B-LBLs, evidence was obtained for ongoing rearrangement of IG light chain variable genes and expression of the surrogate light chain. IGHV mutation analysis showed that all FL-B-LBL pairs harbored identical or near-identical somatic mutations. From the somatic gene alterations found in the IG and non-IG genes, we conclude that the FLs and B-LBLs did not develop in parallel from early t(14;18)-positive IG-unmutated precursors, but that the B-LBLs developed from preexistent FL subclones that accumulated additional genetic damage. |
Databáze: | OpenAIRE |
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