FOXO1

Overview

Mutations in the FOXO1 gene, which encodes a member of the forkhead family of transcription factors, play a significant role in diffuse large B-cell lymphoma (DLBCL). Mutations primarily occur in the first exon, with significant portions affecting the N-terminal region and the Forkhead DNA binding domain.1 These mutations are common in DLBCL, BL and, to a lesser extent, FL.2,3 FOXO1 mutations can contribute to resistance to certain therapies, such as anti-CD20-based immunotherapies, by repressing MS4A1 (CD20) expression.4

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2011-07-27 : Morin : DLBCL 2012-10-04 : Schmitz : BL 2021-07-15 : Duns : PMBL

Relevance tier by entity

Entity Tier Description
MZL 1 high-confidence MZL gene
PMBL 2 relevance in PMBL/cHL/GZL not firmly establisheddunsCharacterizationDLBCLPMBL2021b?
BL 1 high-confidence BL gene1
DLBCL 1 high-confidence DLBCL gene2
FL 1 high-confidence FL gene2

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity source frequency (%)
BL GAMBL genomes+capture 23.33
BL Thomas cohort 28.00
BL Panea cohort 21.80
DLBCL GAMBL genomes 10.13
DLBCL Schmitz cohort 7.23
DLBCL Reddy cohort 2.40
DLBCL Chapuy cohort 2.14
FL GAMBL genomes 12.93

Mutation pattern and selective pressure estimates

Entity aSHM Significant selection dN/dS (missense) dN/dS (nonsense)
BL No Yes 14.841 5.170
DLBCL No No 6.936 0.000
FL No Yes 18.992 103.028

FOXO1 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr13 41240294 C>T R19Q
chr13 41240294 C>G R19P
chr13 41240294 C>A R19L
chr13 41240289 G>C R21G
chr13 41240289 G>A R21C
chr13 41240288 C>T R21H
chr13 41240288 C>G R21P
chr13 41240288 C>A R21L
chr13 41240286 AG>GC S22P
chr13 41240286 AG>GA S22P
chr13 41240286 A>G S22P
chr13 41240285 G>C S22W
chr13 41240281 G>T C23*
chr13 41240280 T>C T24A
chr13 41240279 G>A T24I
chr13 41240277 A>G W25R
chr13 41240275 C>T W25*
chr13 41240274 G>C P26A
chr13 41240274 G>A P26S
chr13 41240273 G>A P26L
chr13 41240271 G>C L27V

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

FOXO1 Expression

References

1.
Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M, Wright G, Shaffer AL, Hodson DJ, Buras E, Liu X, Powell J, Yang Y, Xu W, Zhao H, Kohlhammer H, Rosenwald A, Kluin P, Müller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Ogwang MD, Reynolds SJ, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pittaluga S, Wilson W, Waldmann TA, Rowe M, Mbulaiteye SM, Rickinson AB, Staudt LM. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012 Oct 4;490(7418):116–120. PMCID: PMC3609867
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 SJM, 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. PMCID: PMC3210554

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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