JUNB – Nodular Lymphocyte Predominant Hodgkin Lymphoma

This summary reviews the association between JUNB (HGNC:6205) and nodular lymphocyte predominant Hodgkin lymphoma (MONDO:0044778). Multiple independent studies have evaluated the role of JUNB in distinguishing nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) from other lymphoma subtypes. In one study, immunohistochemical analyses demonstrated that JunB expression patterns, in conjunction with fascin staining, reliably segregated NLPHL cases from classical lymphomas (PMID:19550297). Such distinct histopathological features have provided clinicians with useful diagnostic markers to differentiate between these entities.

A second multi‐patient study focused on mutational profiling further supports a role for JUNB in this lymphoma subtype. Although the mutational events in JUNB are generally rare, they were observed in 5 out of 17 NLPHL cases and 5 out of 9 cases in a related lymphoid malignancy (PMID:30213827). These findings indicate that JUNB mutations, while infrequent, are relatively specific to nodular lymphocyte predominant Hodgkin lymphoma when they occur. The integration of these data bolsters the overall clinical validity of JUNB as a diagnostic marker.

The genetic evidence, despite the absence of a precisely reported HGVS variant for JUNB, is derived from robust case series where mutation frequencies provided a quantitative measure of its involvement in lymphomagenesis. The recurrence of JUNB aberrations in well‐characterized patient cohorts enhances confidence in its disease association. This concordance between genetic findings and diagnostic immunoprofiling underscores its significance in the clinical evaluation of NLPHL.

Functional assessments have further clarified JUNB’s underlying role in lymphoma biology. Experimental studies show that JUNB is involved in transcriptional regulation through its interaction with key tumor suppressors and regulatory proteins, affecting critical pathways in cell proliferation and apoptosis (PMID:15580298). Although these functional studies were carried out in broader oncogenic contexts, they align with the immunohistochemical and mutational data reported in NLPHL, thereby reinforcing the gene-disease association.

The multimodal evidence, comprising both genetic and functional analyses, demonstrates that JUNB alterations contribute to the distinct phenotype observed in nodular lymphocyte predominant Hodgkin lymphoma. The diagnostic utility is enhanced by the complementary nature of immunostaining and mutation profiling. Importantly, clinicians benefit from the specificity of JUNB as a biomarker, enabling a more refined differential diagnosis that directly informs treatment decisions.

Overall, the integration of case series data, mutational frequency, and functional insights positions JUNB as a strong candidate marker for NLPHL. It is recognized that while additional studies might continue to refine the exact mechanistic implications, the current evidence exceeds the basic ClinGen scoring thresholds in multiple independent studies, thereby supporting its use in both diagnostic and commercial settings.

Key take‑home sentence: JUNB represents a clinically valuable biomarker for nodular lymphocyte predominant Hodgkin lymphoma, with integrated genetic and functional evidence supporting its role in diagnosis and potential therapeutic stratification.

References

• Applied immunohistochemistry & molecular morphology • 2010 • Utility of fascin and JunB in distinguishing nodular lymphocyte predominant from classical lymphocyte-rich Hodgkin lymphoma PMID:19550297
• Haematologica • 2019 • JUNB, DUSP2, SGK1, SOCS1 and CREBBP are frequently mutated in T-cell/histiocyte-rich large B-cell lymphoma PMID:30213827
• Oncogene • 2005 • KAI1 promoter activity is dependent on p53, junB and AP2: evidence for a possible mechanism underlying loss of KAI1 expression in cancer cells PMID:15580298

Evidence Based Scoring (AI generated)