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.
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.
Tibiletti
Maria Grazia
MG
Department of Human Morphology, Unit of Pathology, University of Insubria-Ospedale di Circolo, Varese, Italy. mgtibiletti@hotmail.com
Martin
Vittoria
V
Bernasconi
Barbara
B
Del Curto
Barbara
B
Pecciarini
Lorenza
L
Uccella
Silvia
S
Pruneri
Giancarlo
G
Ponzoni
Maurillio
M
Mazzucchelli
Luca
L
Martinelli
Giovanni
G
Ferreri
Andrés J
AJ
Pinotti
Graziella
G
Assanelli
Andrea
A
Scandurra
Marta
M
Doglioni
Claudio
C
Zucca
Emanuele
E
Capella
Carlo
C
Bertoni
Francesco
F
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
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