HLA-A

Overview

Mutations in the HLA-A 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. Different approaches for mapping sequencing data 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. Deletions of this gene are more commonly reported than HLA-A mutations.¹

Relevance tier by entity

Entity	Tier	Description
BL	2	relevance in BL not firmly established
DLBCL	1	high-confidence DLBCL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	7.46
DLBCL	Schmitz cohort	11.06
DLBCL	Reddy cohort	0.20
DLBCL	Chapuy cohort	8.97
BL	GAMBL genomes+capture	1.39
BL	Thomas cohort	1.30
BL	Panea cohort	NA

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	No	No	4.995	22.371
DLBCL	No	Yes	14.841	190.534
FL	No	No	0.000	0.000

## HLA-A Hotspots

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

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

References

1. Riemersma, S., Jordanova, E., Schop, R., Philippo, K., Looijenga, L., Schuuring, E., & Kluin, P. (2000). Extensive genetic alterations of the HLA region, including homozygous deletions of HLA class II genes in B-cell lymphomas arising in immune-privileged sites.. Blood, 96 10, 3569-77 . https://doi.org/10.1182/BLOOD.V96.10.3569.