Table of Contents

Overview

This is one of several genes that encode linker histone proteins that are recurrently mutated in DLBCL and FL.1,2 Mutations are often found in the globular domain of the protein, which is critical for its interaction with DNA and other histone proteins.

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 94 0.0863 [0.0696,0.103]
DLBCL GAMBL with Reddy 2,088 167 0.0800 [0.0683,0.0916]
DLBCL BC 231 20 0.0866 [0.0503,0.1228]
DLBCL Dana-Farber 303 27 0.0891 [0.057,0.1212]
DLBCL NCI 470 40 0.0851 [0.0599,0.1103]
DLBCL Reddy 999 73 0.0731 [0.0569,0.0892]
DLBCL DLBCL_ICGC 85 7 0.0824 [0.0239,0.1408]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 32 0.0498 [0.033,0.0667]
FL GAMBL with Crouch 1,189 61 0.0513 [0.0388,0.0638]
FL BC 379 21 0.0554 [0.0324,0.0784]
FL Kalmbach 164 8 0.0488 [0.0158,0.0817]
FL Crouch 547 29 0.0530 [0.0342,0.0718]
FL FL_ICGC 99 3 0.0303 [0,0.0641]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 11 0.0355 [0.0149,0.0562]
BL GAMBL without ICGC/Zhou 320 12 0.0374 [0.0166,0.0583]
BL GAMBL with Panea 410 15 0.0365 [0.0183,0.0546]
BL BLGSP 219 8 0.0365 [0.0117,0.0614]
BL Zhou/ICGC 90 3 0.0333 [0,0.0704]
BL Panea 101 4 0.0396 [0.0016,0.0776]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 5.8796 27.4064 0.0305
FL 4.5633 0.0000 0.0035
DLBCL 1.6745 0.5573 0.0015

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Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2017-01-26 : Krysiak : FL 2018-05-01 : Chapuy : DLBCL 2021-04-01 : Sarkozy : PMBL

References

1.
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
2.
Krysiak K, Gomez F, White BS, Matlock M, Miller CA, Trani L, Fronick CC, Fulton RS, Kreisel F, Cashen AF, Carson KR, Berrien-Elliott MM, Bartlett NL, Griffith M, Griffith OL, Fehniger TA. Recurrent somatic mutations affecting B-cell receptor signaling pathway genes in follicular lymphoma. Blood. 2017 Jan 26;129(4):473–483. PMCID: PMC5270390
3.
Sarkozy C, Hung SS, Chavez EA, Duns G, Takata K, Chong LC, Aoki T, Jiang A, Miyata-Takata T, Telenius A, Slack GW, Molina TJ, Ben-Neriah S, Farinha P, Dartigues P, Damotte D, Mottok A, Salles GA, Casasnovas RO, Savage KJ, Laurent C, Scott DW, Traverse-Glehen A, Steidl C. Mutational landscape of gray zone lymphoma. Blood. 2021 Apr 1;137(13):1765–1776.

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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