Cytogenetics and molecular cytogenetics in diffuse large B-cell lymphoma (DLBCL)

Abstract

Background. Diffuse large B-cell lymphoma (DLBCL) accounts for up to 40% of all non-Hodgkin's lymphomas diagnosed in the western hemisphere. Determination of the gene expression profile has confirmed the physiological heterogeneity of the disease and defined three molecular prognostic subgroups -germinal center B-cell-like (GCB), activated B-cell-like (ABC) and primary mediastinal B-cell lymphoma (PMBL) -with different gene expression and prognosis. Methods and Results. This review covers current knowledge on the most frequent recurrent cytogenetic and molecular cytogenetic aberrations in molecular DLBCL subgroups. Conclusions. Cytogenetic and molecular cytogenetic techniques used to determine nonrandom chromosomal aberrations in patients with DLBCL have revealed the incidence of frequent cytogenetic aberrations in the subgroups reported, suggesting their potential use for more accurate prognostic stratification of DLBCL, contributing to personalized selection of the most effective therapy.

Diffuse large B‐cell lymphoma and mantle cell lymphoma of the ocular adnexal region, and lymphoma of the lacrimal gland: An investigation of clinical and histopathological features

“…GCB DLBCLs are characterized by B-cell leukaemia ⁄ lymphoma 2 (BCL2) rearrangements and C-reticuloendotheliosis viral oncogene homologue (C-REL) amplifications, whereas ABC DLBCLs are characterized by constitutive activation of the nuclear factor kappa-light-chain enhancer of activated B cells (NFjB) pathway. The activation of the NFjB pathway prevents apoptosis and may explain the fact that ABC DLBCLs respond less well to R-CHOP therapy than GCB DLBCLs (Lossos 2005;Lenz et al 2008b;Lenz & Staudt 2010;Nedomova et al 2012). …”

Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL

“…GCB and non-GCB DLBCL subtypes can also be distinguished using immunohistochemistry (IHC) algorithms based on expression of markers including CD10, BCL6, and MUM-1; these algorithms have demonstrated 71% to 93% concordance with GEP. [11][12][13] Clinical outcomes differ considerably between GCB and non-GCB DLBCL, 6,8,[14][15][16] with overall survival (OS) significantly inferior in non-GCB patients (5-year OS rates: 16%-64% vs 59%-76% GCB). 3,7,17 Standard frontline treatment of DLBCL is rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) 18,19 ; however, outcomes with R-CHOP are inferior in non-GCB vs GCB DLBCL.…”

“…1,2 Gene expression profiling (GEP) has identified at least 3 molecularly distinct DLBCL subtypes based on differential expression of genes involved in B-cell development, [3][4][5][6][7][8][9][10] including activated B-cell-like (ABC), germinal center B-cell-like (GCB), and unclassified subtypes. GCB and non-GCB DLBCL subtypes can also be distinguished using immunohistochemistry (IHC) algorithms based on expression of markers including CD10, BCL6, and MUM-1; these algorithms have demonstrated 71% to 93% concordance with GEP.…”

A Novel Non-Immunoglobulin (non-Ig)/BCL6 Translocation in Diffuse Large B-Cell Lymphoma Involving Chromosome 10q11.21 Loci and Review on Clinical Consequences of BCL6 Rearrangements

“…This malignancy is characterized by wide variability in clinical outcome and high genetic heterogeneity [1,2]. The most common chromosomal abnormality in DLBCL is a 3q27 translocation affecting BCL6 gene, occurring in up to 45 % of patients [3][4][5][6].…”

“…This zinc-finger transcription factor functions as a sequence-specific transcriptional repressor [8][9][10]. BCL6 is commonly translocated in DLBCL with diverse partners, including one of three immunoglobulin gene (IGH, IGK, IGL) loci [11][12][13] or diverse non-Ig chromosomal loci [3,5,6,14]. The translocations affecting the BCL6 gene occur in DLBCL Marie Jarosova and Eva Kriegova contributed equally to this work.…”