FBXO11

Overview

Somatic mutations in FBXO11 are common in BL^1,2 and appear in a small number of DLBCLs.³ This gene has some recurrent sites of mutations (hot spots). Mutations lead to stabilization of BCL6, an important transcriptional repressor involved in lymphomagenesis.⁴ These mutations present a potential novel target for therapeutic intervention, particularly through strategies aimed at degrading BCL6 or inhibiting its function.⁴

History

Mutations in this gene were first described in BL in 2015 by Pighi et al⁴ and in DLBCL by Hübschmann et al.⁵

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

Relevance tier by entity

Entity	Tier	Description
	2	relevance in MZL not firmly established
	1	high-confidence BL gene
	1	high-confidence DLBCL gene

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

Pighi, C., Compagno, M., Wang, Q., Cheong, T., Poggio, T., Langellotto, F., Celle, P., Zamó, A., & Chiarle, R. (2015). FBXO11, a Regulator of BCL6 Stability, Is Recurrently Mutated in Burkitt Lymphoma. Blood, 126, 3673-3673. https://doi.org/10.1182/BLOOD.V126.23.3673.3673.
Grande BM, Gerhard DS, Jiang A, Griner NB, Abramson JS, Alexander TB, Allen H, Ayers LW, Bethony JM, Bhatia K, Bowen J, Casper C, Choi JK, Culibrk L, Davidsen TM, Dyer MA, Gastier-Foster JM, Gesuwan P, Greiner TC, Gross TG, Hanf B, Harris NL, He Y, Irvin JD, Jaffe ES, Jones SJM, Kerchan P, Knoetze N, Leal FE, Lichtenberg TM, Ma Y, Martin JP, Martin MR, Mbulaiteye SM, Mullighan CG, Mungall AJ, Namirembe C, Novik K, Noy A, Ogwang MD, Omoding A, Orem J, Reynolds SJ, Rushton CK, Sandlund JT, Schmitz R, Taylor C, Wilson WH, Wright GW, Zhao EY, Marra MA, Morin RD, Staudt LM. Genome-wide discovery of somatic coding and noncoding mutations in pediatric endemic and sporadic Burkitt lymphoma. Blood. 2019 Mar 21;133(12):1313-1324. doi: 10.1182/blood-2018-09-871418. Epub 2019 Jan 7. PMID: 30617194; PMCID: PMC6428665.
Thomas N, Dreval K, Gerhard DS, Hilton LK, Abramson JS, Ambinder RF, Barta S, Bartlett NL, Bethony J, Bhatia K, Bowen J, Bryan AC, Cesarman E, Casper C, Chadburn A, Cruz M, Dittmer DP, Dyer MA, Farinha P, Gastier-Foster JM, Gerrie AS, Grande BM, Greiner T, Griner NB, Gross TG, Harris NL, Irvin JD, Jaffe ES, Henry D, Huppi R, Leal FE, Lee MS, Martin JP, Martin MR, Mbulaiteye SM, Mitsuyasu R, Morris V, Mullighan CG, Mungall AJ, Mungall K, Mutyaba I, Nokta M, Namirembe C, Noy A, Ogwang MD, Omoding A, Orem J, Ott G, Petrello H, Pittaluga S, Phelan JD, Ramos JC, Ratner L, Reynolds SJ, Rubinstein PG, Sissolak G, Slack G, Soudi S, Swerdlow SH, Traverse-Glehen A, Wilson WH, Wong J, Yarchoan R, ZenKlusen JC, Marra MA, Staudt LM, Scott DW, Morin RD. Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma. Blood. 2023 Feb 23;141(8):904-916. doi: 10.1182/blood.2022016534. PMID: 36201743; PMCID: PMC10023728.
Pighi, C., Cheong, T., Compagno, M., Patrucco, E., Arigoni, M., Olivero, M., Wang, Q., López, C., Bernhart, S., Grande, B., Poggio, T., Langellotto, F., Bonello, L., Dall’Olio, R., Martínez-Martín, S., Molinaro, L., Celle, P., Whitfield, J., Soucek, L., Voena, C., Calogero, R., Morin, R., Staudt, L., Siebert, R., Zamó, A., & Chiarle, R. (2021). Frequent mutations of FBXO11 highlight BCL6 as a therapeutic target in Burkitt lymphoma.. Blood advances. https://doi.org/10.1182/bloodadvances.2021005682.
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. doi: 10.1038/s41375-021-01251-z. Epub 2021 May 5. PMID: 33953289; PMCID: PMC8257491.