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.
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.
Rimsza
Lisa M
LM
Department of Pathology, University of Arizona, Tucson, AZ 85724-5043, USA. rimsza@ahsc.arizona.edu
Roberts
Robin A
RA
Campo
Elias
E
Grogan
Thomas M
TM
Bea
Silvia
S
Salaverria
Itziar
I
Zettl
Andreas
A
Rosenwald
Andreas
A
Ott
German
G
Muller-Hermelink
H Konrad
HK
Delabie
Jan
J
Fisher
Richard I
RI
Unger
Joseph M
JM
Leblanc
Michael
M
Staudt
Louis M
LM
Jaffe
Elaine S
ES
Gascoyne
Randy D
RD
Chan
Wing C
WC
Weisenburger
Dennis D
DD
Greiner
Timothy
T
Braziel
Rita M
RM
Miller
Thomas P
TP
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
C083728:MHC class II transactivator protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators