HLA-B

Table of Contents

Overview
Relevance tier by entity
Mutation incidence in large patient cohorts (GAMBL reanalysis)
Mutation pattern and selective pressure estimates
HLA-B Hotspots
Expression
References

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.

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene¹
	1	high-confidence DLBCL gene²
	2	relevance in FL not firmly established

Mutation incidence in large patient cohorts (GAMBL reanalysis)

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Mutation pattern and selective pressure estimates

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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*

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Expression

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References

Wienand K, Chapuy B, Stewart C, Dunford AJ, Wu D, Kim J, Kamburov A, Wood TR, Cader FZ, Ducar MD, Thorner AR, Nag A, Heubeck AT, Buonopane MJ, Redd RA, Bojarczuk K, Lawton LN, Armand P, Rodig SJ, Fromm JR, Getz G, Shipp MA. Genomic analyses of flow-sorted Hodgkin Reed-Sternberg cells reveal complementary mechanisms of immune evasion. Blood Adv. 2019 Dec 10;3(23):4065–4080. PMCID: PMC6963251

Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, Cruz-Gordillo P, Knoechel B, Asmann YW, Slager SL, Novak AJ, Dogan A, Ansell SM, Link BK, Zou L, Gould J, Saksena G, Stransky N, Rangel-Escareño C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Hernández-Lemus E, Schwarz-Cruz y Celis A, Imaz-Rosshandler I, Ojesina AI, Jung J, Pedamallu CS, Lander ES, Habermann TM, Cerhan JR, Shipp MA, Getz G, Golub TR. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3879–3884. PMCID: PMC3309757