CIITA

Overview

CIITA encodes the major histocompatibility complex (MHC) class II transactivator. CIITA mutations are frequent in PMBCL. These mutations often include structural genomic rearrangements, missense, nonsense, and frameshift mutations. In PMBCL, these mutations are thought to contribute to loss of MHC expression.¹ Although loss of CIITA and MHC Class II Expression is commonly observed in DLBCL, the role of mutations and methylation affecting this locus remains unclear.² CIITA is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus.

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Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene¹
	1-a	aSHM target and high-confidence DLBCL gene²

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	2.87
DLBCL	Schmitz cohort	6.60
DLBCL	Reddy cohort	4.30
DLBCL	Chapuy cohort	4.27

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	Yes	No	1.029	0.000
DLBCL	Yes	No	0.648	4.031
FL	Yes	No	2.701	0.000

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chr16	10970795	10975465	TSS	active_promoter-strong_enhancer

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

CIITA Expression

References

Mottok A, Woolcock B, Chan FC, Tong KM, Chong L, Farinha P, Telenius A, Chavez E, Ramchandani S, Drake M, Boyle M, Ben-Neriah S, Scott DW, Rimsza LM, Siebert R, Gascoyne RD, Steidl C. Genomic Alterations in CIITA Are Frequent in Primary Mediastinal Large B Cell Lymphoma and Are Associated with Diminished MHC Class II Expression. Cell Rep. 2015 Nov 17;13(7):1418–1431.

Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJM, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298–303. PMCID: PMC3210554