Gene affected:
Interferon regulatory factor 4 (also commonly known as MUM-1)

Clinical significance
IRF4 is overexpressed in a range of lymphoid malignancies in the absence of direct mutation. Specific genetic changes are also recognised:
Chromosomal translocations involving IRF4 are infrequent, but when present bring the gene together with the immunoglobulin heavy or light chain promotors causing overexpression. This is particularly seen in myeloma with t(6;14)(p25;q32), and in a subtype of paediatric and young adult DLBL (described as a distinct subtype in WHO 2016).
Direct mutations may cause IRF4 activation in ATLL, while a broad spectrum of changes are seen in other lymphoid disorders (and other cancers) whose effects variously include missense mutations, nonsense mutations, and silent mutations.

Function of gene

IRF4 is part of the interferon regulatory factor family of transcription factors that typically form part of the response to infection by virus. IRF4 is lymphocyte specific, and is important in the innate and adaptive immune systems where it controls B cell and T cell development

NGS panel gene coverage

The panel covers the full coding sequence. Chr 6p25.3

Occurrence and significance

High expression is very frequent in lymphoid disorders (particularly myeloma), and in many disorders IRF4 is essential to malignant function (IRF4 addiction). However, only a proportion have a mutation.

Translocations involving IRF4 (see Clinical Significance)
These are infrequent, but define a distinct subtype of follicular lymphoma in children
DLBCL IRF4 is mutated in around 10% of all DLBCL
subtypes: 3.6% of ABC, 4.8% of GCB, 11.1% of PMBL
Other NHL (around 2% cases)
The precise functional relevance is unclear
ATLL (up to 50%)
Activating mutations have been reported as having high frequency


GeneWiki link:
Gene Wiki entry for IRF4
1. Occurence in DLBCL
2. In ATLL
3. In myeloma