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Extensive genetic alterations of the HLA region, including homozygous deletions of HLA class II genes in B-cell lymphomas arising in immune-privileged sites.
- Source :
-
Blood [Blood] 2000 Nov 15; Vol. 96 (10), pp. 3569-77. - Publication Year :
- 2000
-
Abstract
- 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.
- Subjects :
- Adolescent
Adult
Aged
Central Nervous System Neoplasms genetics
Central Nervous System Neoplasms immunology
Central Nervous System Neoplasms metabolism
Chromosome Mapping
Chromosomes, Human, Pair 6 genetics
Cytogenetic Analysis
Female
Genes, MHC Class II immunology
HLA-A Antigens genetics
HLA-A Antigens metabolism
HLA-DQ Antigens genetics
HLA-DQ Antigens metabolism
HLA-DR Antigens genetics
HLA-DR Antigens metabolism
Homozygote
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Loss of Heterozygosity
Lymph Nodes pathology
Lymphoma, B-Cell immunology
Lymphoma, Large B-Cell, Diffuse genetics
Lymphoma, Large B-Cell, Diffuse immunology
Lymphoma, Large B-Cell, Diffuse metabolism
Major Histocompatibility Complex immunology
Male
Middle Aged
Testicular Neoplasms genetics
Testicular Neoplasms immunology
Testicular Neoplasms metabolism
Gene Deletion
Genes, MHC Class II genetics
Lymphoma, B-Cell genetics
Major Histocompatibility Complex genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 96
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 11071656