LAZ3 rearrangements in non-Hodgkin's lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients

Abstract

We have recently shown that an evolutionary conserved gene LAZ3, encoding a zinc finger protein, is disrupted and overexpressed in some B-cell lymphomas (mainly with a large cell component) that show chromosomal rearrangements involving 3q27. Because the breakpoints involved in these rearrangements are focused in a narrow major translocation cluster (MTC) on chromosome 3, we used genomic probes from this region to study the molecular rearrangements of LAZ3 in a large series of patients (217) with non-Hodgkin's lymphoma (NHL). Southern blot analysis showed LAZ3 rearrangement in 43 patients (19.8%). Rearrangement was found in 11 of the 84 patients (13%) with follicular lymphoma but was most frequent in aggressive lymphoma (diffuse mixed, diffuse large cell, and large cell immunoblastic subtypes), in which 31 of the 114 patients (27%) were affected. The highest proportion of LAZ3 alteration was observed in B-cell aggressive lymphoma (26 of 71 cases, 37%). Eleven of the 32 patients with 3q27 chromosomal abnormality had no LAZ3 rearrangement, suggesting the possibility of LAZ3 involvement outside the MTC. On the other hand, 18 of the 39 patients with LAZ3 rearrangement and available cytogenetic results did not have visible chromosomal break at 3q27, suggesting that almost a half of the rearrangements are not detectable by cytogenetic methods. No statistical association could be found between LAZ3 status and initial features of the disease or clinical outcome in either follicular or aggressive lymphomas. We conclude that LAZ3 alteration is a relatively frequent event in B-cell lymphoma, especially in those of aggressive histology. It could be used as a genomic marker of the disease, and further studies are needed to clarify clinical implications of these alterations.

Low incidence of BCL‐6 gene alterations for diffuse large B‐cell lymphomas in Taiwan Chinese

“…For the group of patients with low‐grade FL, a gene rearrangement incidence of 6.7% was found. This rate is generally lower compared with Western populations, it is but similar to the findings from Lo Coco et al8 and Bastard et al,25 who demonstrated BCL ‐6 rearrangement in 6–15% of FLs. Furthermore, we also found no transformation of follicular lymphoma in patients with BCL ‐6 gene rearrangement.…”

“…This finding suggests that BCL ‐6 alterations are manifested only in B‐cell NHLs. We identified BCL ‐6 gene rearrangements in samples from 16.9% of patients with DLBCL, an incidence below the 37% and 45% rates reported by Bastard et al25 and Lo Coco et al,8 respectively. The reason for this lower incidence may be due to geographic differences in the pathogenesis of lymphoma or to institutional selection bias.…”

“…Bastard et al found no correlation between BCL ‐6 rearrangement and clinical characteristics in a series of 217 patients with NHL and also found no significant effect of BCL ‐6 rearrangement on survival in 83 survivors of aggressive lymphoma. 25 However, Offit et al proposed that BCL ‐6 rearrangement may serve as a favorable prognostic marker based on the study of 102 patients with DLBCL 27. The loci of chromosomal translocation involving the BCL ‐6 gene also may influence the clinical outcome of patients with DLBCL.…”

Cytogenetic features of de novo CD5‐positive diffuse large B‐cell lymphoma: Chromosome aberrations affecting 8p21 and 11q13 constitute major subgroups with different overall survival

“…Identification of each type of DLBCL not only with the IPI but also with biological prognostic factors that directly show the characteristics of the tumor is essential for the establishment of better standard chemotherapy methods for each type. The biological prognostic factors proposed so far are gene abnormality ( TP53 , BCL6 ), serum protein (nm23H1), surface markers, and gene expression profiles (Bastard et al, 1994; Offit et al, 1994; Ichikawa et al, 1997; Jaffe et al, 2001; Niitsu et al, 2001; Rosenwald et al, 2002; Shipp et al, 2002).…”

Primary follicular lymphoma of the testis in childhood

“…A translocation between the immunoglobin heavy chain region on chromosome 14 and the bcl ‐2 gene on chromosome 18 resulting in overexpression of Bcl‐2 protein is implicated in the pathogenesis of over 85% of follicular lymphomas in adults;17, 18 bcl ‐2 involvement in pediatric follicular lymphomas has not been shown. An oncogenic role for p53 and bcl ‐6 has also been proposed for adult follicular lymphoma,19–23 but analysis of pediatric follicular lymphomas is lacking.…”