title: Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t(14;18), 3q27, or other translocations: t(14;18) and 3q27 are mutually exclusive.
abstract: Chromosomal translocations involving t(14;18)(q32;q21) and the chromosome 3q27 region are common in B-cell non-Hodgkin lymphoma of germinal center cell origin. Grade 3B follicular lymphoma (FL), consisting almost exclusively of centroblasts, is a distinct subgroup of follicular lymphomas that has more in common clinically with the aggressive diffuse large B-cell lymphomas than with their indolent FL grade 1 and 2 counterparts. We studied the cytogenetic and molecular genetic aberrations by classic cytogenetics, polymerase chain reaction, Southern blot hybridization, and fluorescence in situ hybridization, with special emphasis on t(14;18), affecting bcl-2, and 3q27 rearrangement, affecting bcl-6, in 32 cases of FL grade 3B. Three distinctive subgroups were identified based upon the existence of breakpoint 3q27, a translocation t(14;18), or the absence of both. Group I involved a t(14;18) and no 3q27 aberrations (n = 13); group II was without a t(14;18) and without 3q27 aberrations (n = 9), but had other cytogenetic aberrations; and group III was without a t(14;18) but with aberrations involving 3q27 (n = 10). None of the FL grade 3B cases harbored both a t(14;18) and 3q27 aberration. These results, in particular the finding of a mutual exclusiveness of bcl-2 and bcl-6 rearrangement, indicate at least 3 different pathways of oncogenesis in FL grade 3B. FL grade 3B with bcl-2 rearrangement probably is part of the same entity as the other follicular lymphomas (1, 2, 3A), whereas the cases with 3q27 abnormalities or other unrelated translocations are more closely related to the majority of diffuse large-cell lymphomas of germinal center cell origin.
authors.affiliation: Department of Genetics, University Medical Center Groningen, The Netherlands. a.g.bosga-bouwer@medgen.azg.nl
authors.forename: Anneke G
authors.initials: AG
authors.lastname: Bosga-Bouwer
authors.forename: Gustaaf W
authors.initials: GW
authors.lastname: van Imhoff
authors.forename: Ronald
authors.initials: R
authors.lastname: Boonstra
authors.forename: Anneke
authors.initials: A
authors.lastname: van der Veen
authors.forename: Eugenia
authors.initials: E
authors.lastname: Haralambieva
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
authors.forename: Bauke
authors.initials: B
authors.lastname: de Jong
authors.forename: Vanessa
authors.initials: V
authors.lastname: Krause
authors.forename: Martin C
authors.initials: MC
authors.lastname: Palmer
authors.forename: Robert
authors.initials: R
authors.lastname: Coupland
authors.forename: Philip M
authors.initials: PM
authors.lastname: Kluin
authors.forename: Eva
authors.initials: E
authors.lastname: van den Berg
authors.forename: Sibrand
authors.initials: S
authors.lastname: Poppema
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D002893:Chromosomes, Human, Pair 3; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D015321:Gene Rearrangement; D019254:Genes, bcl-2; D006801:Humans; D008224:Lymphoma, Follicular / Q000145:classification / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors