title: A comprehensive genetic and histopathologic analysis identifies two subgroups of B-cell malignancies carrying a t(14;19)(q32;q13) or variant BCL3-translocation.
abstract: The biologic and pathologic features of B-cell malignancies bearing a translocation t(14;19)(q32;q13) leading to a fusion of IGH and BCL3 are still poorly described. Herein we report the results of a comprehensive cytogenetic, fluorescence in situ hybridization (FISH), molecular and histopathological survey of a large series of B-cell malignancies with t(14;19) or variant translocations. A total of 56 B-cell malignancies with a FISH-proven BCL3 involvement were identified with the translocation partners being IGH (n=51), IGL (n=2), IGK (n=2) and a non-IG locus (n=1). Hierarchical clustering of chromosomal changes associated with the t(14;19) indicated the presence of two different groups of IG/BCL3-positive lymphatic neoplasias. The first group included 26 B-cell malignancies of various histologic subtypes containing a relatively high number of chromosomal changes and mostly mutated IgVH genes. This cluster displayed three cytogenetic branches, one with rearrangements in 7q, another with deletions in 17p and a third one with rearrangements in 1q and deletions in 6q and 13q. The second group included 19 cases, mostly diagnosed as B-cell chronic lymphocytic leukemia (B-CLL), and characterized by few additional chromosomal changes (e.g. trisomy 12) and unmutated IgVH genes. In conclusion, our study indicates that BCL3 translocations are not restricted to B-CLL but present in a heterogeneous group of B-cell malignancies.
authors.affiliation: Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel, Christian-Albrechts University, Kiel, Germany.
authors.forename: J I
authors.initials: JI
authors.lastname: Martín-Subero
authors.forename: R
authors.initials: R
authors.lastname: Ibbotson
authors.forename: W
authors.initials: W
authors.lastname: Klapper
authors.forename: L
authors.initials: L
authors.lastname: Michaux
authors.forename: E
authors.initials: E
authors.lastname: Callet-Bauchu
authors.forename: F
authors.initials: F
authors.lastname: Berger
authors.forename: M J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: C
authors.initials: C
authors.lastname: De Wolf-Peeters
authors.forename: M J
authors.initials: MJ
authors.lastname: Dyer
authors.forename: P
authors.initials: P
authors.lastname: Felman
authors.forename: A
authors.initials: A
authors.lastname: Gardiner
authors.forename: R D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: S
authors.initials: S
authors.lastname: Gesk
authors.forename: L
authors.initials: L
authors.lastname: Harder
authors.forename: D E
authors.initials: DE
authors.lastname: Horsman
authors.forename: M
authors.initials: M
authors.lastname: Kneba
authors.forename: R
authors.initials: R
authors.lastname: Küppers
authors.forename: A
authors.initials: A
authors.lastname: Majid
authors.forename: N
authors.initials: N
authors.lastname: Parry-Jones
authors.forename: M
authors.initials: M
authors.lastname: Ritgen
authors.forename: M
authors.initials: M
authors.lastname: Salido
authors.forename: F
authors.initials: F
authors.lastname: Solé
authors.forename: G
authors.initials: G
authors.lastname: Thiel
authors.forename: H-H
authors.initials: HH
authors.lastname: Wacker
authors.forename: D
authors.initials: D
authors.lastname: Oscier
authors.forename: I
authors.initials: I
authors.lastname: Wlodarska
authors.forename: R
authors.initials: R
authors.lastname: Siebert
mesh_terms: D000328:Adult; D000368:Aged; D000081242:B-Cell Lymphoma 3 Protein; D002883:Chromosomes, Human, Pair 14; D002888:Chromosomes, Human, Pair 19; D020732:Cytogenetic Analysis; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006651:Histocytochemistry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015448:Leukemia, B-Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors