HLA B - morinlab/LLMPP GitHub Wiki

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 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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    title Publication timing
      2019-12-10 : Wienand : PMBL

Relevance tier by entity

Entity Tier Description
PMBL 1 high-confidence PMBL/cHL/GZL gene
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

HLA-B Expression

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.
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