Recurrent mutations in genes involved in nuclear factor-κB signalling in nodal marginal zone lymphoma-diagnostic and therapeutic implications.
OBJECTIVE
To investigate the spectrum of mutations in 20 genes involved in B-cell receptor and/or Toll-like receptor signalling resulting in activation of nuclear factor-κB (NF-κB) in 20 nodal marginal zone lymphomas (NMZLs), 20 follicular lymphomas (FLs), and 11 cases of B-cell lymphoma, unclassifiable (BCL-u).


RESULTS
Nodal marginal zone lymphomas were diagnosed according to strict criteria, including the expression of at least one putative marginal zone marker (MNDA and/or IRTA1). Cases that showed features of NMZL but did not fulfil all criteria were included as BCL-u. All FLs were required to have a BCL2 rearrangement. Mutations were found in: nine NMZLs, with recurrent mutations in TNFAIP3 and CD79B; 12 FLs, with recurrent mutations in TNFRSF14, TNFAIP3, and CARD11; and five cases of BCL-u, with recurrent mutations in TNFRSF14. TNFRSF14 mutations were present in FL and BCL-u, but not in any of the NMZLs. In the BCL-u group, TNFRSF14 mutations clustered with a FL immunophenotype.


CONCLUSIONS
These results suggest that TNFRSF14 mutations point towards a diagnosis of FL, and can be used in the sometimes difficult distinction between NMZL and FL, but to apply this in diagnostics would require confirmation in an independent cohort. In addition, the presence or absence of specific mutations in pathways converging on NF-κB could be important for decisions regarding targeted treatment.
Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Michiel
M
van den Brand
Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Jos
J
Rijntjes
Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Konnie M
KM
Hebeda
Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Laura
L
Menting
Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Carolyn V
CV
Bregitha
Department of Haematology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Wendy B C
WB
Stevens
Department of Haematology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Walter J F M
WJ
van der Velden
Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Bastiaan B J
BB
Tops
Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
J Han J M
JH
van Krieken
Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Patricia J T A
PJ
Groenen
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D003937:Diagnosis, Differential; D018572:Disease-Free Survival; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D018442:Lymphoma, B-Cell, Marginal Zone / Q000175:diagnosis / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
D014408:Biomarkers, Tumor; D016328:NF-kappa B; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506028:TNFRSF14 protein, human
TNFAIP3; TNFRSF14; diagnosis; follicular lymphoma; nodal marginal zone lymphoma; non-Hodgkin lymphoma; nuclear factor-κB