Table of Contents

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.

Relevance tier by entity

Entity Tier Description
DLBCL 1 High-confidence DLBCL gene
FL 2 Role of LTB mutations in FL requires confirmation
PMBL 1 High-confidence PMBL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 106 0.0973 [0.0797,0.1149]
DLBCL GAMBL with Reddy 2,088 106 0.0508 [0.0414,0.0602]
DLBCL BC 231 26 0.1126 [0.0718,0.1533]
DLBCL Dana-Farber 303 28 0.0924 [0.0598,0.125]
DLBCL NCI 470 40 0.0851 [0.0599,0.1103]
DLBCL Reddy 999 0 0.0001 [0,7e-04]
DLBCL DLBCL_ICGC 85 12 0.1412 [0.0672,0.2152]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 48 0.0748 [0.0544,0.0951]
FL GAMBL with Crouch 1,189 94 0.0791 [0.0637,0.0944]
FL BC 379 33 0.0871 [0.0587,0.1155]
FL Kalmbach 164 11 0.0671 [0.0288,0.1054]
FL Crouch 547 46 0.0841 [0.0608,0.1074]
FL FL_ICGC 99 4 0.0404 [0.0016,0.0792]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 7 0.0036 [0,0.0102]
BL GAMBL without ICGC/Zhou 320 13 0.0375 [0.0168,0.0583]
BL GAMBL with Panea 410 13 0.0047 [0,0.0112]
BL BLGSP 219 7 0.0320 [0.0087,0.0553]
BL Zhou/ICGC 90 0 0.0011 [0,0.008]
BL Panea 101 6 0.0594 [0.0133,0.1055]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 3.6041 0.0000 1
FL 2.8220 18.5768 0
DLBCL 1.0495 5.3066 0

aSHM regions

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

Visualizations

Protein

View coding variants in ProteinPaint hg19 or hg38

Genome

View all variants in GenomePaint hg19 or hg38

Expression

History

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

References

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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.
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Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA, Lawrence MS, Roemer MGM, Li AJ, Ziepert M, Staiger AM, Wala JA, Ducar MD, Leshchiner I, Rheinbay E, Taylor-Weiner A, Coughlin CA, Hess JM, Pedamallu CS, Livitz D, Rosebrock D, Rosenberg M, Tracy AA, Horn H, van Hummelen P, Feldman AL, Link BK, Novak AJ, Cerhan JR, Habermann TM, Siebert R, Rosenwald A, Thorner AR, Meyerson ML, Golub TR, Beroukhim R, Wulf GG, Ott G, Rodig SJ, Monti S, Neuberg DS, Loeffler M, Pfreundschuh M, Trümper L, Getz G, Shipp MA. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018 May;24(5):679–690. PMCID: PMC6613387
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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;

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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