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| Status |
Public on Jul 19, 2023 |
| Title |
C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [Illumina BeadChip] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Disease-causing mutations in genes encoding transcription factors (TF) are frequent in hematopoietic malignancies and might affect TF-interactions with respective DNA-binding motifs. Here, we report the characterization of a recurrent somatic mutation c.295T>C in the IRF4 gene in classic Hodgkin lymphoma (cHL) leading to a C99R exchange. IRF4-C99R is located in the center of the IRF4 alpha3-recognition helix contacting the DNA 5´-GAAA-3´ IRF consensus sequence. IRF4-C99R fundamentally alters IRF4 DNA-binding, combining loss-of-binding at canonical IRF motifs and neomorph gain-of-binding at canonical and non-canonical IRF composite elements (CEs), in particular AP-1-IRF-CEs (AICEs). In line, IRF4-C99R profoundly impairs IRF4-dependent plasma cell induction, and specifically up-regulates degenerate-AICE-dependent distinct cHL disease-characteristic genes. These data document an unprecedented mutation-induced shift of TF binding specificity and its impact for lymphoma pathogenesis and TF modulation.
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| Overall design |
Illumina BeadChip HT-12 V4.0 expression data from BJAB cells with Tet-inducible control, IRF4WT and IRF4C99R cells treated with 0, 6, 24 and 48 hours doxycycline
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| Contributor(s) |
Schleußner N, Cauchy P, Franke V, Crespo O, Edginton-White B, Assi S, Huber L, Obier N, Cockerill P, Küppers R, Hartmann S, Hansmann ML, Grosschedl R, Bonifer C, Bukur T, Mathas S |
| Citation(s) |
37935654 |
| |
| Submission date |
Aug 23, 2022 |
| Last update date |
Dec 01, 2023 |
| Contact name |
Pierre Daniel Cauchy |
| E-mail(s) |
cauchy@ie-freiburg.mpg.de
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| Phone |
+49 (0)761 270-77576
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| Organization name |
University Medical Center Freiburg
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| Department |
Zentrum für Translationale Zellforschung
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| Lab |
AG Onco-Immunology
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| Street address |
Breisacher Str. 115
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| City |
Freiburg |
| State/province |
Baden-Württemberg |
| ZIP/Postal code |
79106 |
| Country |
Germany |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE211445 |
C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma |
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| Relations |
| BioProject |
PRJNA872553 |
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