BCL6 - morinlab/LLMPP GitHub Wiki

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BCL6

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.

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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

Relevance tier by entity

Entity	Tier	Description
	2	Although recurrent, the relevance of mutations in BL is tenuous [@loveGeneticLandscapeMutations2012]
	1-EE[@balSuperenhancerHypermutationAlters2022]	high-confidence DLBCL gene [@morinFrequentMutationHistonemodifying2011; @morinMutationalStructuralAnalysis2013; @reddyGeneticFunctionalDrivers2017; @schmitzGeneticsPathogenesisDiffuse2018a]
	1	high-confidence FL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	5.08
BL	Thomas cohort	3.40
BL	Panea cohort	7.90
DLBCL	GAMBL genomes	11.66
DLBCL	Schmitz cohort	10.85
DLBCL	Reddy cohort	6.41
DLBCL	Chapuy cohort	5.13
FL	GAMBL genomes	5.77

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	Yes	No	7.427	0.000
DLBCL	Yes	Yes	25.672	60.803
FL	Yes	Yes	27.215	62.162

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