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

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Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 108 0.0992 [0.0814,0.1169]
DLBCL GAMBL with Reddy 2,088 110 0.0527 [0.0431,0.0623]
DLBCL BC 231 22 0.0952 [0.0574,0.1331]
DLBCL Dana-Farber 303 28 0.0924 [0.0598,0.125]
DLBCL NCI 470 52 0.1106 [0.0823,0.139]
DLBCL Reddy 999 2 0.0020 [0,0.0048]
DLBCL DLBCL_ICGC 85 6 0.0706 [0.0161,0.125]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 6 0.0193 [0.0039,0.0346]
BL GAMBL without ICGC/Zhou 320 6 0.0187 [0.0039,0.0336]
BL GAMBL with Panea 410 8 0.0194 [0.006,0.0327]
BL BLGSP 219 4 0.0183 [5e-04,0.036]
BL Zhou/ICGC 90 2 0.0222 [0,0.0527]
BL Panea 101 2 0.0198 [0,0.047]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 9 0.0140 [0.0049,0.0231]
FL GAMBL with Crouch 1,189 18 0.0151 [0.0082,0.0221]
FL BC 379 9 0.0237 [0.0084,0.0391]
FL Kalmbach 164 0 0.0006 [0,0.0044]
FL Crouch 547 9 0.0165 [0.0058,0.0271]
FL FL_ICGC 99 0 0.0010 [0,0.0073]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 5.5829 30.9870 1.0000
FL 1.2070 34.0072 0.0018
DLBCL 11.2823 116.9391 0.0000

HLA-A Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr6 29910596 T>A F46I
chr6 29910609 G>A G50D

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Expression

History

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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.
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.
3.
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

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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