Table of Contents

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. The relevance of CIITA mutations in DLBCL remains unclear. Selective pressure analysis did not identify this gene as significantly enriched for either missense or truncating mutations, indicating that many of these mutations may represent passengers.

Experimental Evidence

Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a reduction or loss of function (LOF).1

Relevance tier by entity

Entity Tier Description
DLBCL 1 High-confidence DLBCL gene
PMBL 1 High-confidence PMBL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 51 0.0468 [0.0343,0.0594]
DLBCL GAMBL with Reddy 2,088 94 0.0450 [0.0361,0.0539]
DLBCL BC 231 3 0.0130 [0,0.0276]
DLBCL Dana-Farber 303 15 0.0495 [0.0251,0.0739]
DLBCL NCI 470 31 0.0660 [0.0435,0.0884]
DLBCL Reddy 999 43 0.0430 [0.0305,0.0556]
DLBCL DLBCL_ICGC 85 2 0.0235 [0,0.0558]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 20 0.0312 [0.0177,0.0446]
FL GAMBL with Crouch 1,189 39 0.0328 [0.0227,0.0429]
FL BC 379 10 0.0264 [0.0102,0.0425]
FL Kalmbach 164 7 0.0427 [0.0117,0.0736]
FL Crouch 547 19 0.0347 [0.0194,0.0501]
FL FL_ICGC 99 3 0.0303 [0,0.0641]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 0.6435 0.0000 1.0000
FL 3.1728 2.7062 1.0000
DLBCL 1.2138 2.1121 0.2378

aSHM regions

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

Visualizations

Protein

View coding variants in ProteinPaint hg19 or hg38

Genome

View all variants in GenomePaint hg19 or hg38

Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2011-07-27 : Morin : DLBCL 2015-11-17 : Mottok : PMBL

References

1.
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.
2.
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

Citing

If you use the information or data from this site, please cite

Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.

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