Characterisation of BCL2-JH rearrangements in follicular lymphoma: PCR detection of 3 ' BCL2 breakpoints and evidence of a new cluster

Follicular lymphomas (FL) are closely associated with a t(14;18)(q32;q21) t ranslocation, leading to a bcl2 protein overproduction. This translocation probably constitutes a very early step in the development of the disease. B esides the cytogenetic assay, t(14;18) detection can be achieved using eith er Southern blot or polymerase chain reaction (PCR). Since 1990, several pu blications have reported discrepancies between the results of cytogenetic a nd molecular analysis of t(14;18). Using methods able to explore long DNA f ragments, several authors reported breakpoints located outside the usual br eakpoint regions. However, these techniques cannot be easily used in routin e. The aim of this study was to develop a simple PCR assay to amplify rearr angements usually not detected in FL. We selected a group of 83 patients wi th a t(14;18) on cytogenetic analysis: using usual probes and primers, 54/8 3 (65.1%) showed a MBR rearrangement, 7/83 (8.4%) were mcr positive and 22/ 83 (26.5%) remained negative. Among these 22 rearrangements, nine could be detected using this new PCR assay. Four breakpoints were located in a 20 bp area suggesting a recurrent breakpoint cluster close to an Alu repetitive sequence. Finally, remaining negative cases (13/83, 15.6%) suggest that oth er breakpoints are located between the MBR and mcr regions.