BCL1/PRAD1 is the gene locus involved in the t(11;14)(q13;q32) translocation, which often occurs in a proposed subtype of non-Hodgkin's lymphoma of B-cell phenotype (B-NHL), named mantle cell lymphoma (MCL).
The t(11;14) breakpoint junctions involving the bcl-1 major translocation cluster were amplified by PCR in 4 of 11 (36%) MCL cases and in none of the MCL-PC or SLL cases.
We and others have previously shown that the BCL1 locus is rearranged in 55% to 60% of MCL patients and that, on chromosome 11, more than 80% of the breakpoints are localized within a 1-kbp DNA segment known as the major translocation cluster (MTC).
These lesions include c-myc translocation and p53 inactivation in small noncleaved-cell lymphoma, and bcl-2 and bcl-1 translocation in follicular (FL) and mantle-zone lymphoma, respectively.
These lesions include c-myc translocation and p53 inactivation in small noncleaved-cell lymphoma, and bcl-2 and bcl-1 translocation in follicular (FL) and mantle-zone lymphoma, respectively.
Approximately 70% of centrocytic (mantle-cell) lymphomas have the chromosomal translocation t(11;14) (q13; q32) and associated rearrangements at the bcl-1 breakpoint locus and at the cyclin D1 (PRAD1, CCND1) gene, thus implicating this gene in the pathogenesis of centrocytic lymphoma.
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]).
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]).
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]).
We found oncogene rearrangements in five of the 14 cases: bcl-1 rearrangement on one mantle zone lymphoma, bcl-2 rearrangements in two follicular lymphomas, and c-myc rearrangements in two small noncleaved cell lymphomas.
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.
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.
From these findings and from data available in the literature the conclusion can be drawn that p53 gene mutations at codons 158 and 167 may be associated with lymphoproliferative disorders and that low- or intermediate-grade NHL, including leukemic mantle cell lymphoma, may frequently carry this genetic change.
However, no mutations were detected in exons 5-9 in this case. p53 expression was also detected in 10% of the cells in an additional large cell type of MCL and in less than 1% of the cells in 6 typical cases.