title: Loss of major histocompatibility class II expression in non-immune-privileged site diffuse large B-cell lymphoma is highly coordinated and not due to chromosomal deletions.
abstract: Decreased major histocompatibility class II (MHCII) expression is associated with poor survival in diffuse large B-cell lymphoma (DLBCL). Immune-privileged site DLBCL (IP-DLBCL) patients reportedly have frequent large deletions at the MHCII locus whereas the mechanism of decreased expression in non-IP-DLBCL is unknown. Gene expression profiling data were used for correlation analyses between expression levels of MHCII genes with each other and their transcriptional regulator, CIITA. Comparative genomic hybridization (CGH) assessed chromosomal alterations at MHCII-related loci. Finally, a map was created of expression of genes that are telomeric, within, or centromeric to the MHCII locus. Correlation coefficients among MHCII genes ranged from 0.73 to 0.92, whereas those between adjacent and intervening genes were lower (-0.12 to 0.49). Correlations between MHCII and CIITA expression were higher (0.53 to 0.60) than between CIITA and neighboring genes (-0.05 to 0.22). In 23 MHCII(-) cases, CGH detected 2 losses and 2 gains at MHCII loci. Expression of genes telomeric, within, and centromeric to MHCII loci were near normal in most MHCII(-) cases. Large deletions of the MHCII locus are uncommon in non-IP-DLBCL, implicating altered transcription as the operative mechanism for decreased expression.
authors.affiliation: Department of Pathology, University of Arizona, Tucson, AZ 85724-5043, USA. rimsza@ahsc.arizona.edu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.forename: Robin A
authors.initials: RA
authors.lastname: Roberts
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Grogan
authors.forename: Silvia
authors.initials: S
authors.lastname: Bea
authors.forename: Itziar
authors.initials: I
authors.lastname: Salaverria
authors.forename: Andreas
authors.initials: A
authors.lastname: Zettl
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: H Konrad
authors.initials: HK
authors.lastname: Muller-Hermelink
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Unger
authors.forename: Michael
authors.initials: M
authors.lastname: Leblanc
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Timothy
authors.initials: T
authors.lastname: Greiner
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Miller
mesh_terms: D002503:Centromere / Q000235:genetics; D002872:Chromosome Deletion; D015973:Gene Expression Regulation, Leukemic; D005802:Genes, MHC Class II / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D040641:Quantitative Trait Loci / Q000235:genetics*; D016615:Telomere / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: C083728:MHC class II transactivator protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators