title: BCL2, BCL6, MYC, MALT 1, and BCL10 rearrangements in nodal diffuse large B-cell lymphomas: a multicenter evaluation of a new set of fluorescent in situ hybridization probes and correlation with clinical outcome.
abstract: Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. Although it is a curable disease, fewer than half of patients are cured with conventional chemotherapy. The highly variable outcome reflects a heterogeneous group of tumors, with different genetic abnormalities and responses to therapy. We analyzed 74 cases of diffuse large B-cell lymphoma using interphase fluorescent in situ hybridization with commercially available probes for split-signal targeting BCL-2, BCL-6, MYC, BCL-10, and MALT-1. Gene rearrangements were identified in 48 (65%) of 74 cases. BCL-6 was the most rearranged gene (45%), followed by BCL-2 (21%), BCL-10 (18%), and MYC (16%). No MALT-1 rearrangements were found. When diffuse large B-cell lymphoma cases were subdivided into germinal-center B-cell-like and activated B-cell-like groups, an inverse pattern of BCL-2 and BCL-6 rearrangements was observed. Of interest, the presence of chromosome rearrangements was associated with a worse prognosis. The pattern of cytogenetic abnormalities highlighted the fact not only that diffuse large B-cell lymphoma is a heterogeneous entity but also that even individual cases may contain subclones bearing different chromosomal rearrangements. The relevance and the clinical implication of minor clones showing gene rearrangements are poorly understood; however, this first observation suggests that different rearrangements may be involved in the progression of the disease. The fluorescent in situ hybridization analysis with the panel used in this study is useful to detect the heterogeneity of diffuse large B-cell lymphomas and identify alterations with prognostic implications.
authors.affiliation: Department of Human Morphology, Unit of Pathology, University of Insubria-Ospedale di Circolo, Varese, Italy. mgtibiletti@hotmail.com
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Tibiletti
authors.forename: Vittoria
authors.initials: V
authors.lastname: Martin
authors.forename: Barbara
authors.initials: B
authors.lastname: Bernasconi
authors.forename: Barbara
authors.initials: B
authors.lastname: Del Curto
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pecciarini
authors.forename: Silvia
authors.initials: S
authors.lastname: Uccella
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pruneri
authors.forename: Maurillio
authors.initials: M
authors.lastname: Ponzoni
authors.forename: Luca
authors.initials: L
authors.lastname: Mazzucchelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: Ferreri
authors.forename: Graziella
authors.initials: G
authors.lastname: Pinotti
authors.forename: Andrea
authors.initials: A
authors.lastname: Assanelli
authors.forename: Marta
authors.initials: M
authors.lastname: Scandurra
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zucca
authors.forename: Carlo
authors.initials: C
authors.lastname: Capella
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoni
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000074018:B-Cell CLL-Lymphoma 10 Protein; D014408:Biomarkers, Tumor / Q000235:genetics; D020169:Caspases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein