PMID- 11071656
OWN - NLM
STAT- MEDLINE
DCOM- 20010111
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 96
IP  - 10
DP  - 2000 Nov 15
TI  - Extensive genetic alterations of the HLA region, including homozygous deletions 
      of HLA class II genes in B-cell lymphomas arising in immune-privileged sites.
PG  - 3569-77
AB  - In B-cell lymphomas, loss of human leukocyte antigen (HLA) class I and II 
      molecules might contribute to immune escape from CD8(+) and CD4(+) cytotoxic T 
      cells, especially because B cells can present their own idiotype. Loss of HLA 
      expression and the possible underlying genomic alterations were studied in 28 
      testicular, 11 central nervous system, and 21 nodal diffuse large B-cell 
      lymphomas (DLCLs), the first two sites are considered as immune-privileged sites. 
      The analysis included immunohistochemistry, loss of heterozygosity analysis, and 
      fluorescent in situ hybridization (FISH) on interphase cells and isolated DNA 
      fibers. Total loss of HLA-A expression was found in 60% of the extranodal cases 
      and in 10% of the nodal cases (P <.01), whereas loss of HLA-DR expression was 
      found in 56% and 5%, respectively (P <.01). This was accompanied by extensive 
      loss of heterozygosity within the HLA region in the extranodal DLCLs. In 3 cases, 
      retention of heterozygosity for D6S1666 in the class II region suggested a 
      homozygous deletion. This finding was confirmed by interphase FISH that showed 
      homozygous deletions in the class II genes in 11 of the 18 extranodal lymphomas 
      but in none of the 7 nodal DLCLs (P <.001). Mapping by fiber FISH showed variable 
      deletions that always included HLA-DQ and HLA-DR genes. Hemizygous deletions and 
      mitotic recombinations often involving all HLA genes were found in 13 of 18 
      extranodal and 2 of 7 nodal lymphomas. In conclusion, a structural loss of HLA 
      class I and II expression might help the B-cell lymphoma cells to escape from 
      immune attack.
FAU - Riemersma, S A
AU  - Riemersma SA
AD  - Department of Pathology, Leiden University Medical Center, Leiden, The 
      Netherlands. s.a.riemersma@lumc.nl
FAU - Jordanova, E S
AU  - Jordanova ES
FAU - Schop, R F
AU  - Schop RF
FAU - Philippo, K
AU  - Philippo K
FAU - Looijenga, L H
AU  - Looijenga LH
FAU - Schuuring, E
AU  - Schuuring E
FAU - Kluin, P M
AU  - Kluin PM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DR Antigens)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Central Nervous System Neoplasms/genetics/immunology/metabolism
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 6/genetics
MH  - Cytogenetic Analysis
MH  - Female
MH  - *Gene Deletion
MH  - Genes, MHC Class II/*genetics/immunology
MH  - HLA-A Antigens/genetics/metabolism
MH  - HLA-DQ Antigens/genetics/metabolism
MH  - HLA-DR Antigens/genetics/metabolism
MH  - Homozygote
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Loss of Heterozygosity
MH  - Lymph Nodes/pathology
MH  - Lymphoma, B-Cell/*genetics/immunology
MH  - Lymphoma, Large B-Cell, Diffuse/genetics/immunology/metabolism
MH  - Major Histocompatibility Complex/*genetics/immunology
MH  - Male
MH  - Middle Aged
MH  - Testicular Neoplasms/genetics/immunology/metabolism
EDAT- 2000/11/09 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/09 11:00
PHST- 2000/11/09 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/09 11:00 [entrez]
AID - S0006-4971(20)48299-0 [pii]
PST - ppublish
SO  - Blood. 2000 Nov 15;96(10):3569-77.