HLA A - morinlab/LLMPP GitHub Wiki

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HLA-A

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.

History

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timeline
    title Publication timing
      2019-08-20 : Desch : PMBL

Relevance tier by entity

Entity	Tier	Description
	2	relevance in PMBL/cHL/GZL not firmly established[@deschGenotypingCirculatingTumor2020]
	1	high-confidence DLBCL gene [@lohrDiscoveryPrioritizationSomatic2012a]

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