PMID- 12756506
OWN - NLM
STAT- MEDLINE
DCOM- 20030911
LR  - 20181113
IS  - 0093-7711 (Print)
IS  - 0093-7711 (Linking)
VI  - 55
IP  - 4
DP  - 2003 Jul
TI  - Mutations in the HLA class II genes leading to loss of expression of HLA-DR and 
      HLA-DQ in diffuse large B-cell lymphoma.
PG  - 203-9
AB  - Loss of expression of human leukocyte antigen (HLA) class II molecules on tumor 
      cells affects the onset and modulation of the immune response through lack of 
      activation of CD4+ T lymphocytes. Previously, we showed that the frequent loss of 
      expression of HLA class II in diffuse large B-cell lymphoma (DLBCL) of the testis 
      and the central nervous system (CNS) is mainly due to homozygous deletions in the 
      HLA region on chromosome band 6p21.3. A minority of cases showed hemizygous 
      deletions or mitotic recombination, implying that mutation of the remaining copy 
      of the class II genes might be involved. Here, we studied three DLBCLs with loss 
      of HLA-DQ expression for mutations in the DQB1 and DQA1 genes and three tumors 
      with loss of HLA-DR expression for mutations in the DRB1 and DRA genes. In one 
      case, a point mutation in exon 2 of the DQB1 gene, leading to the formation of a 
      stop codon, was detected at position 47. In a second case, a stop codon was found 
      at position 11 due to a deletion of 19 bp in exon 1 of the DRA gene. No mutations 
      were found in the promoter sequences of the DRA, DQA1 and DQB1 genes. We conclude 
      that both homozygous deletions and hemizygous deletions or mitotic recombination 
      with mutations of the remaining allele may lead to loss of expression of the HLA 
      class II genes, which is comparable to the mechanisms affecting HLA class I 
      expression in solid cancers.
FAU - Jordanova, Ekaterina S
AU  - Jordanova ES
AD  - Department of Pathology (L1-Q), P1-37, Leiden University Medical Center, 
      Albinusdreef 2, 2333 ZA Leiden, The Netherlands. k.jordanova@lumc.nl
FAU - Philippo, Katja
AU  - Philippo K
FAU - Giphart, Marius J
AU  - Giphart MJ
FAU - Schuuring, Ed
AU  - Schuuring E
FAU - Kluin, Philip M
AU  - Kluin PM
LA  - eng
PT  - Journal Article
DEP - 20030517
PL  - United States
TA  - Immunogenetics
JT  - Immunogenetics
JID - 0420404
RN  - 0 (Codon, Terminator)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DR alpha-Chains)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Base Sequence
MH  - Codon, Terminator/genetics
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/genetics
MH  - Gene Expression
MH  - *Genes, MHC Class II
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DQ alpha-Chains
MH  - HLA-DQ beta-Chains
MH  - HLA-DR Antigens/*genetics
MH  - HLA-DR alpha-Chains
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Lymphoma, B-Cell/*genetics/*immunology
MH  - Lymphoma, Large B-Cell, Diffuse/*genetics/*immunology
MH  - Male
MH  - *Mutation
MH  - Point Mutation
MH  - Recombination, Genetic
MH  - Sequence Deletion
EDAT- 2003/05/21 05:00
MHDA- 2003/09/13 05:00
CRDT- 2003/05/21 05:00
PHST- 2003/01/15 00:00 [received]
PHST- 2003/03/06 00:00 [revised]
PHST- 2003/05/21 05:00 [pubmed]
PHST- 2003/09/13 05:00 [medline]
PHST- 2003/05/21 05:00 [entrez]
AID - 10.1007/s00251-003-0563-z [doi]
PST - ppublish
SO  - Immunogenetics. 2003 Jul;55(4):203-9. doi: 10.1007/s00251-003-0563-z. Epub 2003 
      May 17.