title: Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma.
abstract: Structural aberrations of the short arm of chromosome 2, mostly resulting in gains of 2p13 approximately 16, have recently been described as being highly recurrent in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). As these gains consistently lead to increased copy numbers of the REL oncogene locus, we investigated the expression of the c-Rel protein in a series of 30 cHL cases with known genomic REL status as determined by comparative genomic hybridization and interphase cytogenetics. Expression of the c-Rel protein was investigated in 26 biopsies by immunohistochemistry. Distinct patterns were observed in HRS cells with no staining, cytoplasmic, and/or nuclear staining for c-Rel. All 13 samples with additional copies of the REL locus displayed nuclear staining for c-Rel, while 13 cHL samples lacking chromosome 2 (2p) gains displayed a significantly lower proportion or complete absence of HRS cells with nuclear c-Rel expression. Detailed analysis using combined immunophenotyping and interphase cytogenetics of individual HRS cells demonstrated that REL gains correlated with the presence of nuclear c-Rel staining. Additionally, in 2 cHL samples with translocation breakpoints in 2p13 approximately 16, nuclear staining of c-Rel was observed; in one of them the staining pattern was indicative of a truncated c-Rel protein. The correlation between structural aberrations involving the REL locus and nuclear c-Rel accumulation in HRS cells qualifies REL as a target gene of the frequent gains in 2p in cHL. The data suggest that REL aberrations are a genetic mechanism contributing to constitutive nuclear factor (NF)-kappa B/Rel activation in cHL.
authors.affiliation: Abteilung für Pathologie des Universitätsklinikums Ulm, Germany.
authors.forename: Thomas F E
authors.initials: TF
authors.lastname: Barth
authors.forename: Josée I
authors.initials: JI
authors.lastname: Martin-Subero
authors.forename: Stefan
authors.initials: S
authors.lastname: Joos
authors.forename: Christiane K
authors.initials: CK
authors.lastname: Menz
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hasel
authors.forename: Gunhild
authors.initials: G
authors.lastname: Mechtersheimer
authors.forename: Reza M
authors.initials: RM
authors.lastname: Parwaresch
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Peter
authors.initials: P
authors.lastname: Möoller
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002869:Chromosome Aberrations; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics* / Q000648:ultrastructure; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020573:Genes, rel; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D007668:Kidney / Q000166:cytology / Q000196:embryology; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D014066:Palatine Tonsil / Q000378:metabolism / Q000473:pathology; D020569:Proto-Oncogene Proteins c-rel / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000378:metabolism; D016037:Single-Blind Method; D014162:Transfection; D014178:Translocation, Genetic
chemical_list: D016328:NF-kappa B; D009363:Neoplasm Proteins; D020569:Proto-Oncogene Proteins c-rel; D011993:Recombinant Fusion Proteins