Follicle center lymphoma is associated with significantly elevated levels of BCL-6 expression among lymphoma subtypes, independent of chromosome 3q27 rearrangements

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Abstract
The BCL-6 gene, located on chromosome 3q27, is implicated in the normal germinal center formation and is frequently rearranged in a wide spectrum of lymphomas. However the links between genetic alterations and expression of the gene are not clearly determined. We established a quantitative RT-PCR assay based on TaqMan technology to quantify BCL-6 mRNA expression in different subtypes of lymphomas and to compare the level of expression in lymphomas characterized by the presence or absence of BCL-6 translocation. Total RNA was extracted from 105 nodes biopsies (35 diffuse large B cell lymphomas (DLBCL); 26 follicle center lymphomas (FCL); 7 marginal zone lymphomas (MZL); 6 mantle cell lymphomas (MCL); 6 chronic lymphocytic leukemia (CLL); 5 T cell lymphomas (TCL); 7 classical Hodgkin diseases (HD); 6 nodal metastasis (NM); and 7 reactive hyperplasia (RH)). BCL-6 gene rearrangement was assessed by Southern blot analysis in 75% of 3q27+ DLBCL (n = 20) cases and 67% of 3q27+ cases (n = 10). The highest level of relative BCL-6 expression was observed in FCL (9.12 ± 7.28) comparatively to the other lymphoma subtypes including DLBCL (2.53 ± 1.82; P < 0.001), MCL (1.23 ± 0.73), MZL (1.49 ± 1.3), HD (1.60 ± 1.00), TCL (1.75 ± 1.64), but also RH (3.91 ± 3.12) or NM (1.95 ± 2.6). Among the 26 FCL cases, we observed a lower expression in grade 3 (n = 8) than in grade 1/2 (P < 0.001). Conversely, we failed to show any difference between 3q27+ DLBCL and 3q27−DLBCL cases (P = 0.42). Paradoxically BCL-6 expression in 3q27+ FCL (n = 10) was significantly lower than in 3q27− FCL cases (P = 0.035). Finally, this study showed that BCL-6 expression in lymphoma is largely independent of chromosome 3q27 rearrangement and is more related to the histological subtype. Clinical implication and alternative deregulation pathways of BCL-6 expression remain to be determined.