Immunohistochemical analysis of DLCL and FL biopsy samples showed that the BCL-6 protein is detectable in these tumors independent of the presence of BCL-6 gene rearrangements.
We report here that, in 22/30 (73%) DLCL and 7/15 (47%) follicular lymphoma (FL), but not in other tumor types, the BCL6 gene is also altered by multiple (1.4 x 10(-3) -1.6 x 10(-2) per bp), often biallelic, mutations clustering in its 5' noncoding region.
Of the total of 32 BCL6(+) patients, six carried both BCL2 and BCL6 rearrangements; five of these six showed clinicopathological properties characteristic of follicular lymphoma, suggesting that the presence of the two genetic abnormalities does not necessarily have synergistic effects on malignant phenotypes.
The protein is also widely expressed in NHL: all follicular lymphomas tested showed a pattern of expression similar to the reactive B follicle, independently of the presence of BCL-6 gene rearrangement and/or 3q27 anomalies.
Rearrangement of BCL6 was observed in 6.4 to 14.3% of follicular lymphomas and 28.6 to 35.5% of diffuse large cell lymphomas; regarding the latter, a Japanese series showed a lower incidence.
Although rearrangement of the BCL6 gene is the most frequent genetic change among diffuse lymphomas and some follicular lymphomas this is the first report of a patient with MCL associated with BCL6 rearrangement.
To understand the functional consequence of the chromosomal translocations, we have studied the patterns of expression of the promoters found juxtaposed to BCL6 in DLCL and FL during B-lineage differentiation.
To elucidate the role of the BCL-6 gene alterations in the histological transformation and clonal progression of FL, we analyzed serial biopsy specimens from 12 patients with FL.
All FL tested were bcl-6+ (19) and CD138- (22) with 16/19 also bcl-2 and CD10+ (classic phenotype), one bcl2+, CD10- (grade III) and two bcl2-, CD10+ (grade II or III).
These mutations accumulating in the regulatory region of the BCL-6 gene could play a role in lymphoma progression and in the transformation of follicular lymphomas to more aggressive large cell lymphomas.(Blood.2000;95:1400-1405)
Here, Kostas Stamatopoulos and colleagues relate the molecular data about immunoglobulin genes and the protooncogenes BCL2 and BCL6 to the pathogenesis and evolution of follicular lymphoma.
Bcl-6 mRNA and protein are frequently expressed in the transformed counterparts of the germinal center B-cells, diffuse large B-cell lymphoma and follicular lymphoma, irrespective of the gene rearrangements.
The Bcl-6/CD10 coexpression was observed in 35 DLBCLs (34%) and 14 FLs (82%), and most of them showed a pattern of Bcl-6 expression similar to that of the GC.
Polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE) and direct DNA sequencing were used to identify mutations in the 5' noncoding region of the BCL-6 gene in a total of 40 cases of diffuse large-cell lymphoma (DLCL) and follicular lymphoma (FL).
To evaluate the possible effect of this polymorphism on gene expression, BCL-6 mRNA levels in nine FCL tumors with the 397G-G genotype and in nine FCL tumors with the 397G-C genotype were measured by quantitative real-time RT-PCR.
Follicle center lymphoma is associated with significantly elevated levels of BCL-6 expression among lymphoma subtypes, independent of chromosome 3q27 rearrangements.
We did not find significant differences in survival between patients with FL who showed exclusively bcl-6 mutations and those without bcl-6 mutations, but those patients with a high International Progostic Index score and p53 mutations showed the lowest overall survival (p = 0.002).
We correlated this with the immunohistochemical expression of CD10, bcl2 and bcl6, markers which are usually expressed by the neoplastic cells in follicular lymphomas.