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
| Entity | Tier | Description |
|---|---|---|
 |
1 | high-confidence PMBL/cHL/GZL gene |
 |
2 | relevance in MZL not firmly established3 |
 |
1 | high-confidence DLBCL gene1,4 |
 |
1 | high-confidence FL gene2 |
Mutation incidence in large patient cohorts (GAMBL reanalysis)
| Entity | source | frequency (%) |
|---|---|---|
| BL | GAMBL genomes+capture | 3.23 |
| BL | Thomas cohort | 4.70 |
| BL | Panea cohort | 4.00 |
| DLBCL | GAMBL genomes | 6.12 |
| DLBCL | Schmitz cohort | 5.74 |
| DLBCL | Reddy cohort | 6.11 |
| DLBCL | Chapuy cohort | 7.69 |
| FL | GAMBL genomes | 3.23 |
Mutation pattern and selective pressure estimates
| Entity | aSHM | Significant selection | dN/dS (missense) | dN/dS (nonsense) |
|---|---|---|---|---|
| BL | No | No | 8.064 | 0 |
| DLBCL | No | No | 2.458 | 0 |
| FL | No | No | 0.857 | 0 |
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1.
Morin RD, Mungall K, Pleasance E, Mungall AJ,
Goya R, Huff RD, Scott DW, Ding J, Roth A, Chiu R, Corbett RD, Chan FC,
Mendez-Lago M, Trinh DL, Bolger-Munro M, Taylor G, Hadj Khodabakhshi A,
Ben-Neriah S, Pon J, Meissner B, Woolcock B, Farnoud N, Rogic S, Lim EL,
Johnson NA, Shah S, Jones S, Steidl C, Holt R, Birol I, Moore R, Connors
JM, Gascoyne RD, Marra MA. Mutational and structural analysis of diffuse
large B-cell lymphoma using whole-genome
sequencing. Blood. 2013 Aug 15;122(7):1256–1265. PMCID: PMC3744992
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.
Jallades L, Baseggio L, Sujobert P, Huet S,
Chabane K, Callet-Bauchu E, Verney A, Hayette S, Desvignes JP, Salgado
D, Levy N, Béroud C, Felman P, Berger F, Magaud JP, Genestier L, Salles
G, Traverse-Glehen A. Exome sequencing identifies recurrent
BCOR alterations and the absence of KLF2,
TNFAIP3 and MYD88 mutations in splenic diffuse
red pulp small B-cell lymphoma.
Haematologica. 2017 Oct;102(10):1758–1766. PMCID: PMC5622860
4.
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