FISH analysis with a YAC probe improves detection of LAZ3/BCL6 rearrangement in non-Hodgkin's lymphoma.

Abstract

Chromosomal translocations involving the chromosome 3q27 region are common in B-cell non-Hodgkin's lymphoma (NHL), mainly diffuse large cell lymphoma (DLCL) and less often in follicular lymphoma. Most of these rearrangements involve the same major translocation cluster (MTC) on the 3q27 region, disrupting the LAZ3/BCL6 gene. Some of those translocations are difficult to detect by cytogenetic analysis and/or Southern-blot analysis. In the present report we used a FISH assay to improve the detection of LAZ3/BCL6 rearrangements. We isolated a YAC clone (803g3), containing the BCL6 gene, in order to analyze by FISH 19 cases of B-cell non-Hodgkin's lymphoma with cytogenetically detectable 3q27 rearrangement, including reciprocal translocation in 11 cases, deletion in two cases, and addition of undefined chromosomal material on 3q27 in six cases. In the 11 cases with reciprocal translocation, FISH results confirmed cytogenetic data and showed disruption of the LAZ3 region: four t(3;4)(q27;p13), two t(3;11)(q27;q23.1), four t(3;14)(q27;q32) and one t(2;3)(p12;q27). In two of the cases, reciprocal t(3;14) was associated with other cytogenetically detectable abnormalities of 3q27, but FISH showed that they did not affect the LAZ3 gene region. FISH demonstrated a reciprocal translocation with LAZ3 gene rearrangement in two of the six patients with add 3q27: one t(3;11) and one t(3;14). In the two patients with del(3q27), one had two 3q27 FISH signals and one had only one 3q27 FISH signal, but no LAZ3 gene rearrangement was observed. We have identified a YAC containing the LAZ3/BCL6 gene. This YAC probe could be useful in clinical practice to demonstrate LAZ3 rearrangements by FISH analysis on tumor samples in NHL.