Table of Contents

Overview

Mutations in the HLA-B gene have been associated with a loss of cell surface expression of HLA class I molecules, which are essential for presenting tumor antigens to cytotoxic T cells. This is a common mechanism of immune escape in DLBCL. Deletions of this gene are more commonly reported than HLA-B mutations. The mutation pattern in DLBCL implies the preferential accumulation of inactivating mutations. Different analytical strategies relating to the mapping of sequencing data and subtracting common germline variants can complicate the detection of mutations in this and other HLA genes. Likely owing to this, the rate of mutations is highly variable across studies and the true mutation rate has not been firmly established.

Experimental Evidence

Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a reduction or loss of function (LOF).1

Relevance tier by entity

Cannot include /table1_HLA-B.md - does not exist yet

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 135 0.1240 [0.1044,0.1435]
DLBCL GAMBL with Reddy 2,088 147 0.0704 [0.0594,0.0814]
DLBCL BC 231 22 0.0952 [0.0574,0.1331]
DLBCL Dana-Farber 303 30 0.0990 [0.0654,0.1326]
DLBCL NCI 470 77 0.1638 [0.1304,0.1973]
DLBCL Reddy 999 12 0.0120 [0.0053,0.0188]
DLBCL DLBCL_ICGC 85 6 0.0706 [0.0161,0.125]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 12 0.0187 [0.0082,0.0292]
FL GAMBL with Crouch 1,189 36 0.0303 [0.0205,0.04]
FL BC 379 9 0.0237 [0.0084,0.0391]
FL Kalmbach 164 1 0.0061 [0,0.018]
FL Crouch 547 24 0.0439 [0.0267,0.061]
FL FL_ICGC 99 2 0.0202 [0,0.0479]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 4.9468 70.7193 1e-04
FL 3.4862 73.1773 0e+00
DLBCL 3.5180 35.5219 0e+00

HLA-B Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr6 31324659 C>T G50D
chr6 31324659 C>A G50V
chr6 31324642 G>C Q56E
chr6 31324630 A>T F60I
chr6 31324583 C>T W75*
chr6 31324583 C>G W75C
chr6 31324576 G>A Q78*

Cannot include /browser_HLA-B.md - does not exist yet

Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2019-12-10 : Wienand : PMBL

References

1.
Fangazio M, Ladewig E, Gomez K, Garcia-Ibanez L, Kumar R, Teruya-Feldstein J, Rossi D, Filip I, Pan-Hammarström Q, Inghirami G, Boldorini R, Ott G, Staiger AM, Chapuy B, Gaidano G, Bhagat G, Basso K, Rabadan R, Pasqualucci L, Dalla-Favera R. Genetic mechanisms of HLA-I loss and immune escape in diffuse large B cell lymphoma. Proc Natl Acad Sci U S A. 2021 Jun 1;118(22):e2104504118. PMCID: PMC8179151
2.
Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, Cruz-Gordillo P, Knoechel B, Asmann YW, Slager SL, Novak AJ, Dogan A, Ansell SM, Link BK, Zou L, Gould J, Saksena G, Stransky N, Rangel-Escareño C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Hernández-Lemus E, Schwarz-Cruz y Celis A, Imaz-Rosshandler I, Ojesina AI, Jung J, Pedamallu CS, Lander ES, Habermann TM, Cerhan JR, Shipp MA, Getz G, Golub TR. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3879–3884. PMCID: PMC3309757
3.
Wienand K, Chapuy B, Stewart C, Dunford AJ, Wu D, Kim J, Kamburov A, Wood TR, Cader FZ, Ducar MD, Thorner AR, Nag A, Heubeck AT, Buonopane MJ, Redd RA, Bojarczuk K, Lawton LN, Armand P, Rodig SJ, Fromm JR, Getz G, Shipp MA. Genomic analyses of flow-sorted Hodgkin Reed-Sternberg cells reveal complementary mechanisms of immune evasion. Blood Adv. 2019 Dec 10;3(23):4065–4080. PMCID: PMC6963251

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.

Disclaimer

The content in these pages has been populated, in part, by an automated process. Although we have scrutinized every page to ensure accuracy, errors will inevitably exist. If you find an error please report it as an issue and we will address it.

License

This work is licensed under a Creative Commons Attribution 4.0 International License.

You are free to:

Share — copy and redistribute the material in any medium or format for any purpose, even commercially.

Adapt — remix, transform, and build upon the material for any purpose, even commercially. The licensor cannot revoke these freedoms as long as you follow the license terms.