Extensive genetic alterations of the HLA region, including homozygous deletions of HLA class II genes in B-cell lymphomas arising in immune-privileged sites
| Autor: | Sa, Riemersma, Ekaterina S. Jordanova, Rf, Schop, Philippo K, Lh, Looijenga, Schuuring E, Pm, Kluin |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Lymphoma B-Cell Adolescent HLA-A Antigens Genes MHC Class II Homozygote Chromosome Mapping Loss of Heterozygosity HLA-DR Antigens Middle Aged Immunohistochemistry Central Nervous System Neoplasms Major Histocompatibility Complex Testicular Neoplasms HLA-DQ Antigens Cytogenetic Analysis Humans Chromosomes Human Pair 6 Female Lymph Nodes Lymphoma Large B-Cell Diffuse Gene Deletion In Situ Hybridization Fluorescence Aged |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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