β2-microglobulin aberrations in diffuse large B-cell lymphoma of the testis and the central nervous system

✍ Scribed by Ekaterina S. Jordanova; Sietske A. Riemersma; Katja Philippo; Ed Schuuring; Philip M. Kluin

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: French
• Weight: 233 KB
• Volume: 103
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.10824

✦ Synopsis

Abstract

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, β~2~‐microglobulin (β~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 β~2~m expression for mutations in the latter gene by direct sequencing. Frame shift mutations in repetitive sequences within the β~2~m gene leading to loss of functional β~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 β~2~m gene in both cases but also hemizygous deletions and monosomies in 6 additional cases. Since similar mutations in the β~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 β~2~m mutations. Our data indicate that multiple mechanisms lead to downregulation of β~2~m and concomitant loss of HLA class I expression in DLBCL. © 2002 Wiley‐Liss, Inc.