Rearrangement and overexpression of CCND1 (BCL1/PRAD1), a member of the cyclin G1 gene family, are consistent features of t(11q13)-bearing B-lymphoid tumors (particularly mantle-cell lymphoma [MCL]).
Cytogenetics and molecular biology studies may therefore prove useful, because some of these disorders are associated with non-random abnormalities, such as the t(11;14)(q13;q32) translocation and bcl-1 rearrangement mainly observed in mantle-cell lymphoma (MCL).
In particular, the recognition of chromosomal translocations which have activated the BCL1 and BCL2 proto-oncogenes have strong associations with specific types of non-Hodgkin's malignant lymphomas such as mantle cell lymphoma and follicular center cell lymphoma, respectively.
The t(11;14)(q13;q32) translocation, which juxtaposes the BCL1 oncogene with the Ig heavy chain locus, has been associated with an uncommon subtype of non-Hodgkin's lymphoma (NHL) termed mantle cell lymphoma (MCL).
However, the levels of expression are much lower than in MCLs, and this expression is not associated with bcl-1 rearrangements or PRAD-1/CCND1 gene amplification.
These results indicated that positive nuclear staining of lymphoma cells by 5D4 antibody reflects PRAD1/cyclin D1 mRNA expression, and showed that this monoclonal antibody has diagnostic value for differentiating MCL from other types of lymphomas.
Mantle cell lymphomas (MCLs) are typically CD5-expressing B-cell non-Hodgkin's lymphomas (NHLs) that frequently harbor the chromosomal translocation t(11;14) or bcl-1 gene rearrangements.
In particular, the recognition of chromosomal translocations which have activated the BCL1 and BCL2 proto-oncogenes have strong associations with specific types of non-Hodgkin's malignant lymphomas such as mantle cell lymphoma and follicular center cell lymphoma, respectively.
BCL1 major translocation cluster gene rearrangements had been previously documented in two MCL patients; the other MCL and the two B-SLL, showed no detectable BCL1 or cyclin D1 rearrangements.
The polymerase chain reaction (PCR) was employed to study bcl-1 and immunoglobulin heavy chain (IgH) gene rearrangements (B-cell clonality) using formalin-fixed tissue from 12 cases of MCL.
Rearrangements at the bcl-1 MTC were detected in 13 (39%) of 33 cases of mantle cell lymphoma by PCR and in 13 (48%) of 27 cases by restriction analysis.
A significantly higher frequency (P < 0.05) of allele 2 at the -308-basepair TNF-alpha gene polymorphism was also observed in MCL patients (0.18) compared with endemic control subjects (0.069), again associated with a high relative risk of disease (RR = 3.5; P < 0.05) even in the heterozygous condition.
Cyclin D3 was never detected in any of the samples tested, whereas cyclin D1 was expressed in only the 3 cases (1 LPL and 2 MCL) bearing a t(11;14) translocation.
Rearrangements at the bcl-1 MTC were detected in 13 (39%) of 33 cases of mantle cell lymphoma by PCR and in 13 (48%) of 27 cases by restriction analysis.
Rearrangements at the bcl-1 MTC were detected in 13 (39%) of 33 cases of mantle cell lymphoma by PCR and in 13 (48%) of 27 cases by restriction analysis.
Statistical associations with FAB subtypes were found: aCLL and trisomy 12 (P < 0.00001); mantle zone lymphoma (MZL) and t(11;14) (P < 0.00001) and del(6)(q) (P < 0.0001); CLL/mixed cell type and del(6)(q) (P < 0.002); follicular lymphoma and t(14;18) (P < 0.00001); splenic lymphoma with villous lymphocytes and del(7)(q) (P < 0.0004); leukemic lymphoma (LL) with rearrangements in chromosome 9q (P < 0.0001) and trisomy of 3 (P < 0.001).
Analysis of TNF polymorphisms in Venezuelan ACL patients and endemic unaffected controls demonstrates a high relative risk (RR) of 7.5 (P < 0.001) of MCL disease in homozygotes for allele 2 of a polymorphism in intron 2 of the TNF-beta gene, especially in females (RR = 9.5; P < 0.001) compared with males (RR = 4; P < 0.05).