more refs

-| |2-a | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous |

-| |1-a | aSHM target and high-confidence DLBCL gene |

-## References

-1. *Lazarian, G., Yin, S., Hacken, E., Sewastianik, T., Uduman, M., Font-Tello, A., Gohil, S., Li, S., Kim, E., Joyal, H., Billington, L., Witten, E., Zheng, M., Huang, T., Severgnini, M., Lefebvre, V., Rassenti, L., Gutierrez, C., Georgopoulos, K., Ott, C., Wang, L., Kipps, T., Burger, J., Livak, K., Neuberg, D., Baran-Marszak, F., Cymbalista, F., Carrasco, R., & Wu, C. (2021). A hotspot mutation in transcription factor IKZF3 drives B cell neoplasia via transcriptional dysregulation.. Cancer cell, 39 3, 380-393.e8 . https://doi.org/10.1016/j.ccell.2021.02.003.*

-IRF4 (Interferon Regulatory Factor 4) encodes a transcription factor that plays a critical role in the regulation of immune response genes and B-cell development. Mutations and rearrangements in the IRF4 gene have been implicated in various B-cell lymphomas, including DLBCL. IRF4-rearranged large B-cell lymphomas (LBCL-IRF4) show a unique molecular profile with strong expression of IRF4/MUM1 and are associated with favorable outcomes. MUM1 staining is also commonly used to assign DLBCLs to one of the two cell-of-origin (COO) subgroups by immunohistochemistry.¹ IRF4 is one of [a number of genes](https://github.com/morinlab/LLMPP/wiki/ashm) affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. There are a few mutation hotspots in this gene. The functional role of mutations in IRF4 in the absence of a rearrangement remains poorly understood.

-||2|relevance in PMBL/cHL/GZL not firmly established|

-| |1-a | aSHM target and high-confidence DLBCL gene|

-1. *Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Müller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004 Jan 1;103(1):275-82. doi: 10.1182/blood-2003-05-1545. Epub 2003 Sep 22. PMID: 14504078.*

-2. *Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298-303. doi: 10.1038/nature10351. PMID: 21796119; PMCID: PMC3210554.*

-IRF8 (Interferon Regulatory Factor 8) is a transcription factor critical for the development and function of B lymphocytes. Mutations in IRF8 have been implicated in various lymphoid malignancies, most predominantly in FL and DLBCL. IRF8 is one of [a number of genes](https://github.com/morinlab/LLMPP/wiki/ashm) affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. Coding and non-coding mutations in IRF8 are associated with the EZB subgroup of DLBCL.¹ There is preliminary evidence that IRF8 mutations contribute to immune evasion by downregulating CD74 and HLA-DM in DLBCL.² These are crucial for processing and presentation of self antigens.

-||1|high-confidence PMBL/cHL/GZL gene|

-| |2-a | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous |

-| |1-a | aSHM target and high-confidence DLBCL gene |

-| |1-a | aSHM target and high-confidence FL gene |

-## IRF8 Expression

-

-||2|relevance in PMBL/cHL/GZL not firmly established|

-| |1 |high-confidence DLBCL gene|