Table of Contents

Overview

BCL6 is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. Although common, particularly in DLBCL, the function of many of these mutations remains unclear but some have been shown to affect the regulation of BCL6 expression. The role of BCL6 missense mutations, seen over 9% of patients remains unclear.

Experimental Evidence

Driver mutations affecting this gene in BL/FL/DLBCL have been experimentally demonstrated to cause a reduction or loss of function (LOF).1

Relevance tier by entity

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Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 105 0.0964 [0.0789,0.1139]
DLBCL GAMBL with Reddy 2,088 169 0.0809 [0.0692,0.0926]
DLBCL BC 231 27 0.1169 [0.0755,0.1583]
DLBCL Dana-Farber 303 17 0.0561 [0.0302,0.082]
DLBCL NCI 470 51 0.1085 [0.0804,0.1366]
DLBCL Reddy 999 64 0.0641 [0.0489,0.0792]
DLBCL DLBCL_ICGC 85 10 0.1176 [0.0492,0.1861]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 23 0.0358 [0.0214,0.0502]
FL GAMBL with Crouch 1,189 58 0.0488 [0.0365,0.061]
FL BC 379 15 0.0396 [0.0199,0.0592]
FL Kalmbach 164 3 0.0183 [0,0.0388]
FL Crouch 547 35 0.0640 [0.0435,0.0845]
FL FL_ICGC 99 5 0.0505 [0.0074,0.0936]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 10 0.0309 [0.0116,0.0502]
BL GAMBL without ICGC/Zhou 320 14 0.0349 [0.0149,0.0549]
BL GAMBL with Panea 410 18 0.0366 [0.0185,0.0547]
BL BLGSP 219 6 0.0274 [0.0058,0.049]
BL Zhou/ICGC 90 4 0.0444 [0.0019,0.087]
BL Panea 101 8 0.0792 [0.0265,0.1319]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 4.8417 0.0000 1.0000
FL 4.3398 3.3855 0.6139
DLBCL 6.3126 11.4881 0.0000

aSHM regions

chr_name hg19_start hg19_end region regulatory_comment
chr3 187458526 187464632 TSS NA
chr3 187615533 187625659 Intergenic-1 NA
chr3 187625659 187638101 Intergenic-2 NA
chr3 187657518 187665996 Intergenic-3 NA
chr3 187675741 187690717 Intergenic-4 NA
chr3 187690717 187705000 Intergenic-5 NA

BCL6 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr3 187443373 G>A R585W
chr3 187443370 G>A P586S
chr3 187443369 G>A P586L
chr3 187443367 C>T A587T
chr3 187443366 G>T A587D
chr3 187443366 G>C A587G
chr3 187443345 C>T R594Q
chr3 187443342 A>T I595N

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Expression

Representative Mutations

BL

Rating ★ ★ ★ ★ ☆

All Mutations

BL

1090 747

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2011-07-27 : Morin : DLBCL 2012-12-01 : Love : BL 2013-01-01 : Zhang : DLBCL 2013-08-15 : Morin : DLBCL 2017-10-10 : Reddy : DLBCL 2018-04-12 : Schmitz : DLBCL 2018-05-01 : Chapuy : DLBCL 2021-05-05 : Hubschmann : DLBCL

References

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Reddy A, Zhang J, Davis NS, Moffitt AB, Love CL, Waldrop A, Leppa S, Pasanen A, Meriranta L, Karjalainen-Lindsberg ML, Nørgaard P, Pedersen M, Gang AO, Høgdall E, Heavican TB, Lone W, Iqbal J, Qin Q, Li G, Kim SY, Healy J, Richards KL, Fedoriw Y, Bernal-Mizrachi L, Koff JL, Staton AD, Flowers CR, Paltiel O, Goldschmidt N, Calaminici M, Clear A, Gribben J, Nguyen E, Czader MB, Ondrejka SL, Collie A, Hsi ED, Tse E, Au-Yeung RKH, Kwong YL, Srivastava G, Choi WWL, Evens AM, Pilichowska M, Sengar M, Reddy N, Li S, Chadburn A, Gordon LI, Jaffe ES, Levy S, Rempel R, Tzeng T, Happ LE, Dave T, Rajagopalan D, Datta J, Dunson DB, Dave SS. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. Cell. 2017 Oct;171(2):481–494.e15. PMCID: PMC5659841
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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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