CIITA

Overview

First described 1993. Earliest sequence paper UniProt cites for the protein: Steimle et al, Cell, 1993, "Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome)". Source.

Sources: HGNC HGNC:7067 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P33076 (protein name, function text, keywords and locations (REST API)); CIViC gene CIITA (1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)); Open Targets ENSG00000179583 (association with cancer (MONDO_0004992) 0.64; per-cancer scores at or above 0.5: colorectal cancer 0.52, melanoma 0.56, non-Hodgkin lymphoma 0.50, skin cancer 0.55, lung cancer 0.51 (GraphQL API, CC0)); IntOGen CIITA (driver in 3 cohorts (Act 2, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)

• Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 1 clinical evidence items on its variants. Evidence tier "clinical-evidence" is the strongest of those signals.
• Prevalence not recorded: none of the sources gives a positivity rate.
• Lymphoma, 9p24.1 amplification of CD274, PDCD1LG2 and JAK2: The amplicon contains the genes for both PD-1 ligands and the kinase that induces them, so a single copy-number event raises the ligands twice over, by gene dose and by JAK2-driven transcription (Green 2010). It is the clearest example in oncology of a tumour genetically buying its way out of T-cell attack. Alongside it, CIITA, the master transactivator of MHC class II, is broken by recurrent fusions, which lowers class II on the tumour cell and, in the same rearrangements, places PD-L1 and PD-L2 under new promoters. Frequency: In 108 newly diagnosed classical Hodgkin lymphomas evaluated by fluorescence in situ hybridisation, 97% had concordant alterations of both loci: polysomy in 5% (5 of 108), copy gain in 56% (61 of 108) and amplification in 36% (39 of 108), and higher-level gain predicted shorter progression-free survival (Roemer 2016). Genomic CIITA breaks in 38% of primary mediastinal B-cell lymphomas and 15% of classical Hodgkin lymphomas across 263 B-cell lymphomas (Steidl 2011). What it changes about treatment: Yes, and it is the reason for the sharpest contrast in lymphoma immunotherapy. PD-1 blockade produced an objective response in 20 of 23 heavily pre-treated Hodgkin patients, 87%, in the first study, in a disease where most had already failed both transplant and brentuximab vedotin (Ansell 2015); in B-cell non-Hodgkin lymphoma outside the mediastinal group, single-agent checkpoint blockade does very little. Nothing is tested before a Hodgkin patient is given a checkpoint inhibitor, because the alteration is nearly universal.