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
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
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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