title: Alterations of the CD58 gene in classical Hodgkin lymphoma.
abstract: Immune evasion plays a central role in the pathophysiology of classical Hodgkin lymphoma (cHL). As mutations of the CD58 gene contribute to immune evasion of diffuse large B cell lymphoma tumor cells, we studied whether alterations of the CD58 gene also occur in Hodgkin and Reed/Sternberg (HRS) cells of cHL. Single nucleotide polymorphism chip analysis revealed homozygous deletions within the CD58 gene in two cHL cell lines (SUP-HD1 and U-HO1). Sequencing of the CD58 gene in seven cHL cell lines disclosed in addition a homozygous splice site mutation in cell line KM-H2. None of the three mutated lines expressed CD58 protein on their surface. Thus, three of seven cHL cell lines analyzed harbor destructive CD58 mutations. Molecular analysis of isolated HRS cells from 10 primary cases of cHL; however, did not reveal any case with a CD58 mutation. A FICTION study indicated heterozygous deletions of CD58 in 3 of 13 cHL analyzed. Overall, we report frequent inactivating mutations of CD58 in cHL cell lines, but their rare occurrence in primary HRS cells. As the three cHL cell lines with CD58 mutations were all established from HRS cells located in pleural effusions, i.e., outside the normal lymph node microenvironment, in end-stages of the disease, CD58 inactivation in cHL might be predominantly prevalent to such situations.
authors.affiliation: Faculty of Medicine, Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Faculty of Medicine, Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Institute of Human Genetics, Christian-Albrechts University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Reina
authors.initials: R
authors.lastname: Zühlke-Jenisch
authors.affiliation: Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel/Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.affiliation: Senckenberg Institute of Pathology, University of Frankfurt, Medical School, Frankfurt, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hartmann
authors.affiliation: Senckenberg Institute of Pathology, University of Frankfurt, Medical School, Frankfurt, Germany.
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.affiliation: Institute of Human Genetics, Christian-Albrechts University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.affiliation: Faculty of Medicine, Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.affiliation: Institute of Human Genetics, Christian-Albrechts University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.|Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.|Department of Otolaryngology, Head and Neck Surgery, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Giefing
mesh_terms: D018968:CD58 Antigens / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D019139:Tumor Escape
chemical_list: D018968:CD58 Antigens