Table of Contents

Overview

Mutations in the HLA-C 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-C 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

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

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 50 0.0459 [0.0335,0.0583]
DLBCL GAMBL with Reddy 2,088 50 0.0239 [0.0174,0.0305]
DLBCL BC 231 10 0.0433 [0.017,0.0695]
DLBCL Dana-Farber 303 12 0.0396 [0.0176,0.0616]
DLBCL NCI 470 26 0.0553 [0.0347,0.076]
DLBCL Reddy 999 0 0.0001 [0,7e-04]
DLBCL DLBCL_ICGC 85 2 0.0235 [0,0.0558]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 0.0000 15.7117 1
FL 3.6818 38.8001 1
DLBCL 3.4723 19.9859 0

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 2023-11-15 : Gomez : 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.
Gomez F, Fisk B, McMichael JF, Mosior M, Foltz JA, Skidmore ZL, Duncavage EJ, Miller CA, Abel H, Li YS, Russler-Germain DA, Krysiak K, Watkins MP, Ramirez CA, Schmidt A, Martins Rodrigues F, Trani L, Khanna A, Wagner JA, Fulton RS, Fronick CC, O’Laughlin MD, Schappe T, Cashen AF, Mehta-Shah N, Kahl BS, Walker J, Bartlett NL, Griffith M, Fehniger TA, Griffith OL. Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma. Cancer Res Commun. 2023 Nov 15;3(11):2312–2330. PMCID: PMC10648575

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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