FBXO11

Overview

Somatic mutations in FBXO11 are common in BL¹ and appear in a small number of DLBCLs.² This gene has some recurrent sites of mutations (hot spots). Mutations lead to stabilization of BCL6, an important transcriptional repressor involved in lymphomagenesis. These mutations present a potential novel target for therapeutic intervention, particularly through strategies aimed at degrading BCL6 or inhibiting its function.

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2012-11-11 : Richter : BL 2013-12-13 : Parry : MZL 2018-10-01 : Arthur : DLBCL 2021-05-05 : Hübschmann : DLBCL

Relevance tier by entity

Entity	Tier	Description
	2	relevance in MZL not firmly established³
	1	high-confidence BL gene¹
	1	high-confidence DLBCL gene^2,4

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	23.79
BL	Thomas cohort	21.60
BL	Panea cohort	15.80
DLBCL	GAMBL genomes	3.82
DLBCL	Schmitz cohort	2.13
DLBCL	Reddy cohort	2.10
DLBCL	Chapuy cohort	2.56

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	No	Yes	14.801	114.063
DLBCL	No	Yes	2.464	39.449
FL	No	No	8.837	0.000

FBXO11 hot spots

Chromosome	Coordinate	Mutation	HGVSp
chr2	48040426	T>A	N725I
chr2	48040427	T>C	N725D
chr2	48040427	T>G	N725H
chr2	48040427	T>A	N725Y
chr2	48040488	TA>GC	I704S
chr2	48040489	A>C	I704R
chr2	48040495	T>A	N702I
chr2	48040495	T>C	N702S
chr2	48040496	T>C	N702D
chr2	48040496	T>A	N702Y
chr2	48040500	T>A	E700D
chr2	48040500	T>G	E700D
chr2	48040501	T>A	E700V
chr2	48040510	C>T	G697D
chr2	48040511	C>G	G697R

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

FBXO11 Expression

References

Richter J, Schlesner M, Hoffmann S, Kreuz M, Leich E, Burkhardt B, Rosolowski M, Ammerpohl O, Wagener R, Bernhart SH, Lenze D, Szczepanowski M, Paulsen M, Lipinski S, Russell RB, Adam-Klages S, Apic G, Claviez A, Hasenclever D, Hovestadt V, Hornig N, Korbel JO, Kube D, Langenberger D, Lawerenz C, Lisfeld J, Meyer K, Picelli S, Pischimarov J, Radlwimmer B, Rausch T, Rohde M, Schilhabel M, Scholtysik R, Spang R, Trautmann H, Zenz T, Borkhardt A, Drexler HG, Möller P, MacLeod RAF, Pott C, Schreiber S, Trümper L, Loeffler M, Stadler PF, Lichter P, Eils R, Küppers R, Hummel M, Klapper W, Rosenstiel P, Rosenwald A, Brors B, Siebert R, ICGC MMML-Seq Project. Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing. Nat Genet. 2012 Dec;44(12):1316–1320.

Hübschmann D, Kleinheinz K, Wagener R, Bernhart SH, López C, Toprak UH, Sungalee S, Ishaque N, Kretzmer H, Kreuz M, Waszak SM, Paramasivam N, Ammerpohl O, Aukema SM, Beekman R, Bergmann AK, Bieg M, Binder H, Borkhardt A, Borst C, Brors B, Bruns P, Carrillo de Santa Pau E, Claviez A, Doose G, Haake A, Karsch D, Haas S, Hansmann ML, Hoell JI, Hovestadt V, Huang B, Hummel M, Jäger-Schmidt C, Kerssemakers JNA, Korbel JO, Kube D, Lawerenz C, Lenze D, Martens JHA, Ott G, Radlwimmer B, Reisinger E, Richter J, Rico D, Rosenstiel P, Rosenwald A, Schillhabel M, Stilgenbauer S, Stadler PF, Martín-Subero JI, Szczepanowski M, Warsow G, Weniger MA, Zapatka M, Valencia A, Stunnenberg HG, Lichter P, Möller P, Loeffler M, Eils R, Klapper W, Hoffmann S, Trümper L, ICGC MMML-Seq consortium, ICGC DE-Mining consortium, BLUEPRINT consortium, Küppers R, Schlesner M, Siebert R. Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas. Leukemia. 2021 Jul;35(7):2002–2016. PMCID: PMC8257491

Parry M, Rose-Zerilli MJJ, Gibson J, Ennis S, Walewska R, Forster J, Parker H, Davis Z, Gardiner A, Collins A, Oscier DG, Strefford JC. Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma. PLoS One. 2013;8(12):e83244. PMCID: PMC3862727

Arthur SE, Jiang A, Grande BM, Alcaide M, Cojocaru R, Rushton CK, Mottok A, Hilton LK, Lat PK, Zhao EY, Culibrk L, Ennishi D, Jessa S, Chong L, Thomas N, Pararajalingam P, Meissner B, Boyle M, Davidson J, Bushell KR, Lai D, Farinha P, Slack GW, Morin GB, Shah S, Sen D, Jones SJM, Mungall AJ, Gascoyne RD, Audas TE, Unrau P, Marra MA, Connors JM, Steidl C, Scott DW, Morin RD. Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma. Nat Commun. 2018 Oct 1;9(1):4001. PMCID: PMC6167379