Disease relevance of BRWD2

• A novel member of the WD-repeat gene family, WDR11, maps to the 10q26 region and is disrupted by a chromosome translocation in human glioblastoma cells [1].
• FGFR2 gene on human chromosome 10q26 is amplified in diffuse-type gastric cancer, while WDR11 gene on human chromosome 10q26 is disrupted in glial tumors [2].
• Melanoma cells present a MAGE-3 epitope to CD4(+) cytotoxic T cells in association with histocompatibility leukocyte antigen DR11 [3].
• In this study we have investigated the interaction between two DR11 alleles (DB*1101 and DB*1104) and two previously described tetanus toxin (tt) universal T cell epitopes P2(tt830-843) and P30(tt947-967) by means of a functional cytotoxic competition assay [4].
• Mean index of fibrosis was higher in DR3-positive than in DR11-positive patients (2.14 vs. 1.58; P=.05) [5].

High impact information on BRWD2

• Pretreatment of EahyCIITA with IFN-gamma restored the ability of DR11- or DR13-specific T cells to transmigrate and proliferate, thus abrogating DR-specific retardation [6].
• CONCLUSION: Our results indicate that the presence of the DR11 phenotype is associated with a significantly increased risk for the development of type II MC in patients with chronic HCV infection [7].
• The primary MHC susceptibility allele was found to be DQA2 (Pcorr = 0.0009, RR = 2.5, EF = 35.6), which is in linkage disequilibrium with both DR3 and DR11 [8].
• We have examined peptides bound in vivo to DR alpha beta dimers and alpha beta-Invariant (I) chain complexes purified directly from a DR11, DRw52 homozygous B lymphoblastoid cell line [9].
• The binding of both "monomorphic" and "polymorphic" synthetic DR1 peptides to affinity purified HLA-DR 1 and DR 11 molecules was measured using radiolabeled peptides and high performance size exclusion chromatography [10].

Biological context of BRWD2

• WDR11 is composed of 29 exons distributed over 58 kilobases and oriented towards the telomere [1].
• Positional cloning of this translocation breakpoint resulted in the identification of a novel chromosome 10 gene, WDR11, which is a member of the WD-repeat gene family [1].
• The translocation resulted in deletion of exon 5 and consequently fusion of intron 4 of WDR11 to the 3' untranslated region of a novel member, ZNF320, of the Krüppel-like zinc finger gene family [1].
• FGFR2 and WDR11 are neighboring oncogene and tumor suppressor gene on human chromosome 10q26 [2].
• In this study, we investigated recombination and nucleotide substitution around the WDR11-FGFR2 locus during evolution by using bioinformatics [11].

Anatomical context of BRWD2

• Two analogues, 25R/A and 28E/Q, which bound to soluble DR11 protein, but did not stimulate an anti-DR1-specific T cell clone, inhibited the response of the clone to the wild-type peptide by TCR antagonism [12].
• A human hybridoma monoclonal antibody (TrJ11) recognizing a new HLA-DR epitope shared by DR4, DR8, DR11, and DRB1*1303 [13].

Associations of BRWD2 with chemical compounds

• However, Pl(-)35R clones were resistant to co-trimoxazole, trimethoprim, and eryth- romycin, to which B. cepacia DR11 was also resistant [14].

Analytical, diagnostic and therapeutic context of BRWD2

• Among the 32 ASPs who shared two DR alleles, 5 pairs had both DR8 and DR11, which was significantly more frequent (P < 0.0001) than the incidence in the control group (n = 0) [15].
• DR11 had a frequency lower in type 1 Italian AIH patients than controls (17% vs 35%, P = 0.01) [16].
• HLA typing in this patient revealed A2, A24;B51, B35; Cw4, Cw7; DR9, DR11 [17].

References