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Published on: December 4, 2018
Recurrent mutations in genes involved in nuclear factor-κB signalling in nodal marginal zone lymphoma-diagnostic and
Michiel van den Brand1, Jos Rijntjes1, Konnie M Hebeda1
1Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Aims:
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).
Methods And 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.
Insights
TNFRSF14 mutations are associated with follicular lymphoma (FL) and can help distinguish it from nodal marginal zone lymphoma (NMZL). These findings may guide targeted therapies for B-cell lymphomas.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- B-cell receptor and Toll-like receptor signaling pathways are crucial in lymphomagenesis.
- Nuclear factor-kappa B (NF-κB) activation is a common mechanism in B-cell lymphomas.
- Distinguishing between nodal marginal zone lymphoma (NMZL) and follicular lymphoma (FL) can be challenging.
Purpose of the Study:
- To investigate mutations in 20 genes within NF-κB signaling pathways.
- To analyze mutation spectra in NMZL, FL, and unclassifiable B-cell lymphoma (BCL-u).
- To assess the diagnostic utility of specific mutations in differentiating lymphoma subtypes.
Main Methods:
- Genomic DNA was extracted from 20 NMZLs, 20 FLs, and 11 BCL-u cases.
- A targeted sequencing panel of 20 genes involved in B-cell receptor and Toll-like receptor signaling was employed.
- Immunohistochemistry was used to confirm diagnostic criteria for NMZL and FL, including MNDA, IRTA1, and BCL2 rearrangement.
Main Results:
- Mutations were identified in 9/20 NMZLs (TNFAIP3, CD79B), 12/20 FLs (TNFRSF14, TNFAIP3, CARD11), and 5/11 BCL-u cases (TNFRSF14).
- TNFRSF14 mutations were exclusively found in FL and BCL-u, not in NMZL.
- In BCL-u, TNFRSF14 mutations correlated with a FL immunophenotype.
Conclusions:
- TNFRSF14 mutations are a potential biomarker for distinguishing FL from NMZL.
- These findings may aid in the differential diagnosis of challenging B-cell lymphoma cases.
- Mutation status in NF-κB signaling pathways could inform future targeted treatment strategies.
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