PMID- 12471623 OWN - NLM STAT- MEDLINE DCOM- 20030121 LR - 20220316 IS - 0020-7136 (Print) IS - 0020-7136 (Linking) VI - 103 IP - 3 DP - 2003 Jan 20 TI - Beta2-microglobulin aberrations in diffuse large B-cell lymphoma of the testis and the central nervous system. PG - 393-8 AB - Human leukocyte antigen (HLA) class I molecules are expressed on the surface of all nucleated cells and present antigenic peptides to cytotoxic T cells, thereby playing an important role in initiating the cellular anti-tumor immune response. We previously reported that loss of HLA class I expression in diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) and the testis is a common event. Loss of expression and mutations of the light chain of the HLA class I molecule, beta(2)-microglobulin (beta(2)m) have been described in a variety of human tumors and cell lines. In our study, we screened 15 DLBCL cases with a combined loss of HLA class I and beta(2)m expression for mutations in the latter gene by direct sequencing. Frame shift mutations in repetitive sequences within the beta(2)m gene leading to loss of functional beta(2)m were detected in 2 cases. Loss of heterozygosity (LOH) and fluorescent in situ hybridization (FISH) analysis for chromosome 15 exhibited loss of the remaining copy of the beta(2)m gene in both cases but also hemizygous deletions and monosomies in 6 additional cases. Since similar mutations in the beta(2)m gene have been associated with microsatellite instability (MSI), we used 8 markers to study MSI involvement in DLBCL. Low MSI was more frequent (33%) as compared to nodal DLBCL (n=15) but did not correlate with the beta(2)m mutations. Our data indicate that multiple mechanisms lead to downregulation of beta(2)m and concomitant loss of HLA class I expression in DLBCL. CI - Copyright 2002 Wiley-Liss, Inc. FAU - Jordanova, Ekaterina S AU - Jordanova ES AD - Department of Pathology, Leiden University Medical Center, The Netherlands. k.jordanova@lumc.nl FAU - Riemersma, Sietske A AU - Riemersma SA FAU - Philippo, Katja AU - Philippo K FAU - Schuuring, Ed AU - Schuuring E FAU - Kluin, Philip M AU - Kluin PM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Carrier Proteins) RN - 0 (DNA Primers) RN - 0 (DNA Probes) RN - 0 (DNA-Binding Proteins) RN - 0 (G-T mismatch-binding protein) RN - 0 (HLA Antigens) RN - 0 (MLH1 protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (beta 2-Microglobulin) RN - EC 3.6.1.3 (MSH2 protein, human) RN - EC 3.6.1.3 (MutL Protein Homolog 1) RN - EC 3.6.1.3 (MutS Homolog 2 Protein) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Alleles MH - Brain Neoplasms/*genetics MH - Carrier Proteins MH - *Chromosome Aberrations MH - Chromosome Deletion MH - Chromosomes, Human, Pair 15/genetics MH - DNA Primers/chemistry MH - DNA Probes/genetics MH - DNA-Binding Proteins/metabolism MH - HLA Antigens/genetics MH - Humans MH - Immunoenzyme Techniques MH - In Situ Hybridization, Fluorescence/methods MH - Interphase/genetics MH - Loss of Heterozygosity/*genetics MH - Lymphoma, B-Cell/*genetics MH - Lymphoma, Large B-Cell, Diffuse/*genetics MH - Male MH - Microsatellite Repeats MH - MutL Protein Homolog 1 MH - MutS Homolog 2 Protein MH - Mutation/genetics MH - Neoplasm Proteins/metabolism MH - Nuclear Proteins MH - Proto-Oncogene Proteins/metabolism MH - Testicular Neoplasms/*genetics MH - beta 2-Microglobulin/*genetics/metabolism EDAT- 2002/12/10 04:00 MHDA- 2003/01/22 04:00 CRDT- 2002/12/10 04:00 PHST- 2002/12/10 04:00 [pubmed] PHST- 2003/01/22 04:00 [medline] PHST- 2002/12/10 04:00 [entrez] AID - 10.1002/ijc.10824 [doi] PST - ppublish SO - Int J Cancer. 2003 Jan 20;103(3):393-8. doi: 10.1002/ijc.10824.