title: Combined genetic inactivation of β2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma.
abstract: We report that diffuse large B cell lymphoma (DLBCL) commonly fails to express cell-surface molecules necessary for the recognition of tumor cells by immune-effector cells. In 29% of cases, mutations and deletions inactivate the β2-Microglobulin gene, thus preventing the cell-surface expression of the HLA class-I (HLA-I) complex that is necessary for recognition by CD8(+) cytotoxic T cells. In 21% of cases, analogous lesions involve the CD58 gene, which encodes a molecule involved in T and natural killer cell-mediated responses. In addition to gene inactivation, alternative mechanisms lead to aberrant expression of HLA-I and CD58 in >60% of DLBCL. These two events are significantly associated in this disease, suggesting that they are coselected during lymphomagenesis for their combined role in escape from immune-surveillance.
authors.affiliation: Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA.
authors.forename: Madhavi
authors.initials: M
authors.lastname: Challa-Malladi
authors.forename: Yen K
authors.initials: YK
authors.lastname: Lieu
authors.forename: Olivia
authors.initials: O
authors.lastname: Califano
authors.forename: Antony B
authors.initials: AB
authors.lastname: Holmes
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.forename: Vundavalli V
authors.initials: VV
authors.lastname: Murty
authors.forename: David
authors.initials: D
authors.lastname: Dominguez-Sola
authors.forename: Laura
authors.initials: L
authors.lastname: Pasqualucci
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dalla-Favera
mesh_terms: D018968:CD58 Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D056726:Genetic Association Studies; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D055550:Protein Stability; D014158:Transcription, Genetic; D001613:beta 2-Microglobulin / Q000235:genetics* / Q000378:metabolism
chemical_list: D018968:CD58 Antigens; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin