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β 2 ‐microglobulin aberrations in diffuse large B‐cell lymphoma of the testis and the central nervous system
Author(s) -
Jordanova Ekaterina S.,
Riemersma Sietske A.,
Philippo Katja,
Schuuring Ed,
Kluin Philip M.
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10824
Subject(s) - loss of heterozygosity , biology , primary central nervous system lymphoma , human leukocyte antigen , diffuse large b cell lymphoma , cancer research , beta 2 microglobulin , lymphoma , microbiology and biotechnology , gene , antigen , genetics , immunology , allele
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.