FOXO1 - morinlab/LLMPP GitHub Wiki

bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true nocite: | @dunsCharacterizationDLBCLPMBL2021, @schmitzBurkittLymphomaPathogenesis2012, @morinFrequentMutationHistonemodifying2011

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.[@trinhAnalysisFOXO1Mutations] These mutations are common in DLBCL, BL and, to a lesser extent, FL.[@schmitzBurkittLymphomaPathogenesis2012; @morinFrequentMutationHistonemodifying2011] FOXO1 mutations can contribute to resistance to certain therapies, such as anti-CD20-based immunotherapies, by repressing MS4A1 (CD20) expression.[@pyrzynskaFOXO1PromotesResistance2018]

Experimental Evidence

Driver mutations affecting this gene in FL/DLBCL/BL have been experimentally demonstrated to cause a gain of function (GOF).[@trinhAnalysisFOXO1Mutations]

Relevance tier by entity

include:tables/table1_FOXO1.md

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Mutation pattern and selective pressure estimates

include:tables/dnds_FOXO1.md

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

include:tables/browser_FOXO1.md

Expression

include:tables/mermaid_FOXO1.md