BCL10
Overview
BCL10 (B-cell lymphoma/leukemia 10) is a gene involved in apoptosis signaling and immune response regulation. Mutations in BCL10 have been implicated in the pathogenesis of various lymphomas, particularly mucosa-associated lymphoid tissue (MALT) lymphomas. They have also been reproducibly observed in a smaller proportion of DLBCLs with the frequency in non-MALT lymphomas under some debate. BCL10 mutations are a feature of the BN2 genetic subgroup, mutated in nearly 40% of BN2 cases.1,2
Experimental Evidence
BCL10 missense mutations in the CARD domain and truncating mutations have distinct functions and different effects on BTK and MALT1 inhibitors.3
History
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timeline
title Publication timing
2011-07-27 : Morin : DLBCL
2013-08-15 : Morin : DLBCL
2016-09-08 : Spina : MZL
2017-10-10 : Reddy : DLBCL
2018-04-12 : Schmitz : DLBCL
2018-05-01 : Chapuy : DLBCL
2018-10-01 : Arthur : DLBCL
2023-07-26 : Russler-Germain : FL
Relevance tier by entity
| Entity | Tier | Description |
|---|---|---|
 |
1 | high-confidence MZL genespinaGeneticsNodalMarginal2016b? |
 |
1-EE3 | high-confidence DLBCL gene4,5 |
 |
2 | relevance in FL not firmly establishedrussler-germainMutationsAssociatedProgression2023b? |
Mutation incidence in large patient cohorts (GAMBL reanalysis)
| Entity | source | frequency (%) |
|---|---|---|
| DLBCL | GAMBL genomes | 3.82 |
| DLBCL | Schmitz cohort | 7.66 |
| DLBCL | Reddy cohort | 3.10 |
| DLBCL | Chapuy cohort | 6.41 |
| FL | GAMBL genomes | 2.31 |
| BL | GAMBL genomes+capture | 0.23 |
| BL | Thomas cohort | 0.40 |
| BL | Panea cohort | NA |
Mutation pattern and selective pressure estimates
| Entity | aSHM | Significant selection | dN/dS (missense) | dN/dS (nonsense) |
|---|---|---|---|---|
| BL | No | No | 3.224 | 0.000 |
| DLBCL | No | Yes | 13.754 | 106.692 |
| FL | No | Yes | 0.000 | 223.832 |
BCL10 Hotspots
| Chromosome | Coordinate (hg19) | ref>alt | HGVSp |
|---|---|---|---|
| chr1 | 85736474 | C>T | R58Q |
| chr1 | 85733390 | G>A | Q208* |
| chr1 | 85733386 | A>C | L209* |
View coding variants in ProteinPaint hg19 or hg38
View all variants in GenomePaint hg19 or hg38
BCL10 Expression
References
1.
Wright GW, Huang DW, Phelan JD, Coulibaly ZA,
Roulland S, Young RM, Wang JQ, Schmitz R, Morin RD, Tang J, Jiang A,
Bagaev A, Plotnikova O, Kotlov N, Johnson CA, Wilson WH, Scott DW,
Staudt LM. A
Probabilistic Classification Tool for Genetic
Subtypes of Diffuse Large B Cell Lymphoma with
Therapeutic Implications. Cancer Cell. 2020 Apr
13;37(4):551–568.e14.
2.
Phelan JD, Oellerich T. BCL10
Mutants: Architects of Oncogenic Signaling
Provide a Blueprint for Precision
Medicine. Cancer Discov. 2022 Aug 5;12(8):1844–1846.
3.
Xia
M, David L, Teater M, Gutierrez J, Wang X, Meydan C, Lytle A, Slack GW,
Scott DW, Morin RD, Onder O, Elenitoba-Johnson KSJ, Zamponi N,
Cerchietti L, Lu T, Philippar U, Fontan L, Wu H, Melnick AM. BCL10
Mutations Define Distinct Dependencies Guiding Precision Therapy
for DLBCL. Cancer Discov. 2022 Aug 5;12(8):1922–1941.
PMCID: PMC9357155
4.
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
5.
Morin RD, Mungall K, Pleasance E, Mungall AJ,
Goya R, Huff RD, Scott DW, Ding J, Roth A, Chiu R, Corbett RD, Chan FC,
Mendez-Lago M, Trinh DL, Bolger-Munro M, Taylor G, Hadj Khodabakhshi A,
Ben-Neriah S, Pon J, Meissner B, Woolcock B, Farnoud N, Rogic S, Lim EL,
Johnson NA, Shah S, Jones S, Steidl C, Holt R, Birol I, Moore R, Connors
JM, Gascoyne RD, Marra MA. Mutational and structural analysis of diffuse
large B-cell lymphoma using whole-genome
sequencing. Blood. 2013 Aug 15;122(7):1256–1265. PMCID: PMC3744992
