HLA-B

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.¹ 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.

Relevance tier by entity

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

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	3.46
BL	Thomas cohort	3.80
BL	Panea cohort	5.00
DLBCL	GAMBL genomes	9.18
DLBCL	Schmitz cohort	16.38
DLBCL	Reddy cohort	1.20
DLBCL	Chapuy cohort	10.68
FL	GAMBL genomes	3.46

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	No	Yes	6.598	94.947
DLBCL	No	Yes	27.361	222.398
FL	No	No	0.000	88.288

## 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*

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.