title: BCL6 alternative breakpoint region break and homozygous deletion of 17q24 in the nodular lymphocyte predominance type of Hodgkin's lymphoma-derived cell line DEV.
abstract: DEV is the only cell line derived from nodular lymphocyte predominance type of Hodgkin's lymphoma (NLPHL); however, a comprehensive report about the genetic and immunophenotypic profile of this unique cell line is lacking. We analyzed DEV with respect to immunophenotype and genetic aberrations. The immunostaining revealed positivity for CD45, CD20, CD22, CD79a, IgA2, CD80, CD86, CD74, and BCL6. Cytogenetically, DEV has complex chromosome 3 translocations involving chromosomes 7, 14, and 22. A detailed analysis of the 3q27 breakpoint of the der(3)t(3;14)(p14;q32)t(3;22)(q27;q11.2) revealed a break in the BCL6 alternative breakpoint region. Using array comparative genomic hybridization, a 3-megabase homozygous deletion at 17q24.1-24.2 was identified. Fluorescence in situ hybridization indicated the presence of 2 chromosome 17 homologues, each of which carried a small interstitial deletion. Eight microsatellite markers flanking the homozygously deleted region all showed a homozygous pattern suggesting loss of one of the parental alleles. D17S1809 and D17S1816 could not be amplified using DEV DNA, in keeping with a location within the homozygously deleted segment. In conclusion, DEV has an immunophenotype that is consistent with the neoplastic cells of NLPHL cases, the lymphocytic and histiocytic cells. We demonstrated involvement of the BCL6 gene based on the presence of a breakpoint in the alternative breakpoint region and nuclear staining for BCL6 protein and identified a homozygously deleted region at 17q24.
authors.affiliation: Department of Pathology and Laboratory Medicine, University Medical Centre Groningen and University of Groningen 9700 RB, The Netherlands.
authors.forename: Ciğdem
authors.initials: C
authors.lastname: Atayar
authors.forename: Klaas
authors.initials: K
authors.lastname: Kok
authors.forename: Joost
authors.initials: J
authors.lastname: Kluiver
authors.forename: Anneke
authors.initials: A
authors.lastname: Bosga
authors.forename: Eva
authors.initials: E
authors.lastname: van den Berg
authors.forename: Pieter
authors.initials: P
authors.lastname: van der Vlies
authors.forename: Tjasso
authors.initials: T
authors.lastname: Blokzijl
authors.forename: Geert
authors.initials: G
authors.lastname: Harms
authors.forename: Inge
authors.initials: I
authors.lastname: Davelaar
authors.forename: Birgit
authors.initials: B
authors.lastname: Sikkema-Raddatz
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Martin-Subero
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Sibrand
authors.initials: S
authors.lastname: Poppema
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
mesh_terms: D045744:Cell Line, Tumor; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005819:Genetic Markers; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D051560:Proto-Oncogene Proteins c-bcl-6
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D051560:Proto-Oncogene Proteins c-bcl-6