The t(2;3)(q21;q27) translocation in non-Hodgkin's lymphoma displays BCL6 mutations in the 5' regulatory region and chromosomal breakpoints distant from the gene
The BCL6 gene, mapped at the chromosomal band 3q27,
encodes a POZ/Zinc finger transcription repressor
protein. It is frequently activated in Non-Hodgkin's
lymphomas (NHL) by translocations with breakpoints
clustering in the 5' major breakpoint region (MBR) as
well as by mutations in the same region. The
translocations lead to BCL6 activation by substitution
of promoters of rearranging genes derived from the
reciprocal chromosomal partners such as IG. We report
the molecular genetic analysis of a novel t(2;3)(q21;q27)
translocation subset in NHL comprising three cases
without apparent BCL6 involvement in the translocation.
Southern blot analysis of tumor DNAs utilizing BCL6
MBR probes revealed no rearrangement in two cases.
Two rearranged bands in the third case resulted from a
deletion in one allele and a mutation in the other allele.
Southern blot analysis of DNA from one of the two
tumors without BCL6 rearrangement, using a probe
derived from the recently identified alternative breakpoint region (ABR), showed a rearrangement. The ABR
is located 200-270 kb telomeric to MBR. Mutations
were identified in the previously reported hypermutable
region of BCL6 in all three tumors. In one, the mutant
allele alone was found to be expressed by RT-PCR
analysis of RNA. These results demonstrate the presence
of 3q27 translocation breakpoints at a distance from
BCL6 suggesting distant breaks that deregulate the gene
or involvement of other genes that may be subject to
rearrangement