Hemizygous deletions in the HLA region account for loss of heterozygosity in the majority of diffuse large B-cell lymphomas of the testis and the central nervous system.
Loss of heterozygosity (LOH) is a major mechanism for inactivation of tumor-suppressor genes and has been observed in various solid tumors and lymphomas. The human leukocyte antigen (HLA) region is located at chromosome band 6p21.3, and loss or alteration of this region may provide tumor cells with a mechanism to escape from the immune system. We previously identified small homozygous deletions within the HLA class II region in many of the diffuse large B-cell lymphomas (DLCLs) of the central nervous system (CNS) and the testis. In the present study, we focused on the mechanism leading to LOH in the HLA region. Twenty microsatellite markers, of which 12 were specific for HLA, were applied on 11 extranodal DLCLs of the CNS and 28 of the testis. Additionally, fluorescence in situ hybridization with seven HLA-specific probes and a centromere 6-specific probe was performed on 20 cases to study the mechanism of LOH. In contrast to previously published data on spontaneously mutated lymphoblastoid cell lines, intrachromosomal hemizygous deletion, not mitotic recombination, was the major cause of LOH of the HLA region in these lymphomas. However, opposed to data in colorectal cancer, these deletions were rarely (one of nine cases) associated with an interchromosomal rearrangement such as a translocation.
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. k.jordanova@lumc.nl
Ekaterina S
ES
Jordanova
Sietske A
SA
Riemersma
Katja
K
Philippo
Micheline
M
Giphart-Gassler
Ed
E
Schuuring
Philip M
PM
Kluin
D000483:Alleles; D002872:Chromosome Deletion; D007446:Chromosome Inversion; D020090:Chromosome Segregation / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D015342:DNA Probes / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007399:Interphase / Q000235:genetics; D019656:Loss of Heterozygosity / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D008297:Male; D008938:Mitosis / Q000235:genetics; D009006:Monosomy / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics; D013736:Testicular Neoplasms / Q000235:genetics*; D014178:Translocation, Genetic
D015342:DNA Probes; D006680:HLA Antigens