STAT6
Overview
The STAT6 gene, which encodes a transcription factor involved in the JAK-STAT signaling pathway, plays a significant role in the pathogenesis of various lymphomas, including diffuse large B-cell lymphoma (DLBCL). Below is a summary of the common mutations in the STAT6 gene identified in DLBCL. Mutations in the DNA binding domain of STAT6 are common in PMBCL and more rare in DLBCL.
Relevance tier by entity
| Entity | Tier | Description |
|---|---|---|
| BL | 2 | relevance in BL not firmly established |
| DLBCL | 1 | high-confidence DLBCL gene |
| FL | 1 | high-confidence FL gene |
Mutation incidence in large patient cohorts (GAMBL reanalysis)
| Entity | source | frequency (%) |
|---|---|---|
| BL | GAMBL genomes+capture | 1.62 |
| BL | Thomas cohort | 1.70 |
| BL | Panea cohort | 2.00 |
| DLBCL | GAMBL genomes | 5.74 |
| DLBCL | Schmitz cohort | 2.55 |
| DLBCL | Reddy cohort | 3.80 |
| DLBCL | Chapuy cohort | 4.70 |
| FL | GAMBL genomes | 15.94 |
Mutation pattern and selective pressure estimates
| Entity | aSHM | Significant selection | dN/dS (missense) | dN/dS (nonsense) |
|---|---|---|---|---|
| BL | No | No | 3.301 | 0 |
| DLBCL | No | No | 11.582 | 0 |
| FL | No | Yes | 116.612 | 0 |
## STAT6 Hotspots
Recurrent mutations at the D419 amino acid residue are a common feature in DLBCL, specifically affecting the germinal center B (GCB) cell subtype. These mutations lead to the activation of the JAK/STAT signaling pathway, contributing to lymphomagenesis (Morin et al., 2015).
| Chromosome | Coordinate (hg19) | ref>alt | HGVSp |
|---|---|---|---|
| chr12 | 57496671 | C>G | G416R |
| chr12 | 57496666 | G>T | N417K |
| chr12 | 57496662 | C>T | D419N |
| chr12 | 57496662 | C>G | D419H |
| chr12 | 57496662 | C>A | D419Y |
| chr12 | 57496661 | T>G | D419A |
| chr12 | 57496661 | T>C | D419G |
| chr12 | 57496661 | T>A | D419V |
| chr12 | 57496658 | T>G | N420T |
| chr12 | 57496658 | T>C | N420S |
| chr12 | 57496656 | T>C | N421D |
| chr12 | 57496654 | A>C | N421K |
View coding variants in ProteinPaint hg19 or hg38
View all variants in GenomePaint hg19 or hg38
References
- Morin RD, Assouline S, Alcaide M, Mohajeri A, Johnston RL, Chong L, Grewal J, Yu S, Fornika D, Bushell K, Nielsen TH, Petrogiannis-Haliotis T, Crump M, Tosikyan A, Grande BM, MacDonald D, Rousseau C, Bayat M, Sesques P, Froment R, Albuquerque M, Monczak Y, Oros KK, Greenwood C, Riazalhosseini Y, Arseneault M, Camlioglu E, Constantin A, Pan-Hammarstrom Q, Peng R, Mann KK, Johnson NA. Genetic Landscapes of Relapsed and Refractory Diffuse Large B-Cell Lymphomas. Clin Cancer Res. 2016 May 1;22(9):2290-300. doi: 10.1158/1078-0432.CCR-15-2123. Epub 2015 Dec 8. PMID: 26647218.
Citing
If you use the information or data from this site, please cite
Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.
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