FLUORESCENCE IN-SITU HYBRIDIZATION IDENTIFIES NEW CHROMOSOMAL CHANGESINVOLVING 3Q27 IN NON-HODGKINS-LYMPHOMAS WITH BCL6 LAZ3 REARRANGEMENT/

Twelve B-cell non-Hodgkin's lymphomas with BCL6/LAZ3 rearrangement sel ected from a series of 30 lymphomas with cytogenetically detectable 3q ter abnormalities were characterized at the histological, clinical, an d cytogenetic levels, including fluorescence in situ hybridization (FI SH) analysis, which was performed in all cases but one. A classical t( 3;14) and t(3;22) were found in three patients (25%), In the remaining cases, eleven different 3q27 abnormalities were demonstrated and char acterized with the use of chromosome painting. Seven of twelve ''varia nt'' rearrangements identified in our series affecting 1p32, 1p34, 3p1 4, 6q23, 12p13, 14q11, and 16p13 have not been reported before. Moreov er, involvement of both homologs of chromosome 3 in distinct transloca tions was detected as an unexpected result in two cases and was confir med via FISH in a third case. The putative bichromosomal rearrangement s of the 3q27 region were evidenced by Southern analysis in one of the se cases. In another case, FISH with a cosmid spanning the 3q27 breakp oint region demonstrated the involvement of BCL6/LAZ3 only in one of t wo t(3q27). In our series, which was selected on cytogenetic and molec ular criteria, 50% (6 of 12) of cases with BCL6/LAZ3 rearrangement wer e diagnosed as diffuse, large B-cell lymphomas (DLCL). Another 33% (4 of 12) of cases were diagnosed as follicular center lymphomas (FL), wi th t(14;18)/BCL2 rearrangement in all but one case. Furthermore, in th ree follicular lymphoma cases in which multiple samples were analyzed, the disease showed no evidence of histological progression during a f ollow-up period of 3-14 years. The present data show that rearrangemen t of BCL6 is not restricted to high-grade malignancies as was previous ly suggested but can also occur in low-grade lymphomas. In addition, t he appearance of BCL6/L4Z3 rearrangement in follicular lymphomas is no t related to disease progression. (C) 1995 Wiley-Liss, Inc.