Molecular cytogenetics of IGH rearrangements in non-Hodgkin B-cell lymphoma

Abstract

Rearrangements involving the IGH gene have been identified in about 50% of non-Hodgkin B-cell lymphomas (NHLs) and correlated to clinically relevant subgroups. However, the detection rate largely varied with the technique used. We analyzed the incidence of IGH rearrangements using several fluorescence in situ hybridization (FISH) techniques on metaphases obtained from 96 patients with nodal NHL. An IGH rearrangement was identified in 71 cases (74%). A t(14;18)(q32;q21) was found in 37 of the 42 follicular lymphomas (88.1%) studied and a t(11;14)(q13;q32) in 12 of the 14 mantle cell lymphomas (85.7%). IGH rearrangements were identified in 21 of the 40 diffuse large B-cell lymphomas (52.5%), including seven t(14;18)(q32;q21) and four t(3;14)(q27;q32). Conventional cytogenetics was uninformative in several cases. However, the complemented analysis using 24-color FISH, chromosomal whole paints, telomeric probes and locus specific identifiers enabled us to characterize complex and/or masked IGH translocations in follicular lymphomas and mantle cell lymphomas and to identify all the chromosomal partners involved in IGH rearrangements in diffuse large B-cell lymphomas. This study shows the interest of using metaphase FISH in addition to conventional cytogenetics. Following banding techniques, FISH with the IGH dual color probe can be the first approach in NHL, after which chromosome painting and 24-color FISH can be used to identify the chromosomal partners involved in IGH rearrangements. The identification of these genes is of utmost importance for a better understanding of the molecular mechanisms involved in the genesis of lymphoma.

Prognostic value of chromosomal translocations in small‐bowel diffuse large B‐cell lymphoma

“…It should be noted that we found IGH translocations in 70% of the patients with small‐bowel DLBCL. This incidence is much higher than that observed in previous studies, in which the incidence has been reported to be 25–53% in DLBCLs . Our incidence of IGH translocations in small‐bowel DLBCL was also higher than that seen in cases of gastric DLBCL in our previous study (32%) .…”

MYC/BCL6 double‐hit lymphoma (DHL): a tumour associated with an aggressive clinical course and poor prognosis

“…In contrast, similar data on MYC/BCL6 DHL is limited: case reports and a few case-series are available in the literature totalling approximately 40 cases. 18,[22][23][24][31][32][33][34][35] BCL6 is a transcriptional repressor, whereas BCL2 is an inhibitor of apoptosis. As BCL2 and BCL6 have different functions, it seems reasonable to hypothesize that patients with MYC/ BCL6 DHL may have clinicopathological features that differ from MYC/BCL2 DHL patients.…”

Chromosome abnormalities in diffuse large B‐cell lymphomas: analysis of 231 Chinese patients

“…The t(8;14)(q24;q32) translocation has been found in 5–15% of DLBCL cases , but we found this translocation in only 4.3% of DLBCL cases. Recurrent translocations involving IGH were also found in other studies . In our study, t(3;14)(q27;q32)(12.2%) was the most frequently observed translocation mutation according to cytogenetic analysis, which suggested that IGH (14q32) was the most frequent translocation with BCL6 (3q27).…”