LTB

Overview

LTB (Lymphotoxin Beta) is a member of the tumor necrosis factor (TNF) superfamily, which plays a role in the development and organization of secondary lymphoid tissues and in the regulation of immune responses. LTB 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 the mutation incidence is relatively high in DLBCL, little is known about the role of these mutations in lymphomagenesis. The mutation pattern overall implies a selective pressure to acquire loss-of-function mutations in LTB.

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2018-05-01 : Chapuy : DLBCL 2019-08-20 : Desch : PMBL

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene¹
	1-a	aSHM target and high-confidence DLBCL gene^{chapuyMolecularSubtypesDiffuse2018b?}
	1-a	aSHM target and high-confidence FL gene
	2-a	aSHM target; Although recurrent, the relevance of mutations in BL is tenuous²

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	9.37
DLBCL	Schmitz cohort	8.51
DLBCL	Reddy cohort	NA
DLBCL	Chapuy cohort	9.83
FL	GAMBL genomes	8.78
BL	GAMBL genomes+capture	3.00
BL	Thomas cohort	3.00
BL	Panea cohort	5.90

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
DLBCL	Yes	No	2.261	10.402
FL	Yes	No	5.259	35.735
BL	Yes	No	4.330	0.000

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chr6	31548325	31550717	intron-1	enhancer

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

LTB Expression

References

Desch AK, Hartung K, Botzen A, Brobeil A, Rummel M, Kurch L, Georgi T, Jox T, Bielack S, Burdach S, Classen CF, Claviez A, Debatin KM, Ebinger M, Eggert A, Faber J, Flotho C, Frühwald M, Graf N, Jorch N, Kontny U, Kramm C, Kulozik A, Kühr J, Sykora KW, Metzler M, Müller HL, Nathrath M, Nüßlein T, Paulussen M, Pekrun A, Reinhardt D, Reinhard H, Rössig C, Sauerbrey A, Schlegel PG, Schneider DT, Scheurlen W, Schweigerer L, Simon T, Suttorp M, Vorwerk P, Schmitz R, Kluge R, Mauz-Körholz C, Körholz D, Gattenlöhner S, Bräuninger A. Genotyping circulating tumor DNA of pediatric Hodgkin lymphoma. Leukemia. 2020 Jan;34(1):151–166.

Panea R, Love C, Shingleton JR, Reddy A, Bailey J, Moormann A, Otieno J, Ong’echa J, Oduor C, Schroêder K, Masalu N, Chao N, Agajanian M, Major M, Fedoriw Y, Richards K, Rymkiewicz G, Miles R, Alobeid B, Bhagat G, Flowers C, Ondrejka S, Hsi E, Choi W, Au-Yeung R, Hartmann W, Lenz G, Meyerson H, Lin YY, Zhuang Y, Luftig M, Waldrop A, Dave T, Thakkar D, Sahay H, Li G, Palus B, Seshadri V, Kim S, Gascoyne R, Levy S, Mukhopadhyay M, Dunson D, Dave S. The whole genome landscape of Burkitt lymphoma subtypes. Blood. 2019;