Characterizing Atypical BCL6 Signal Patterns Detected by Digital Fluorescence In Situ Hybridization (FISH) Analysis

The BCL6 gene encodes a 706-amino acid sequence-specific repressor transcription factor [1]. BCL6 has been identified as commonly rearranged in 20–40% of diffuse large B cell lymphomas (DLBCL) [2, 3]. BCL6 can be rearranged with the immunoglobulin (Ig) gene loci or non-Ig gene partners [2]. Break-apart (BAP) FISH probes are widely used for clinical testing of genes with multiple translocation partners [4]. The expected signal pattern of a rearranged sample using a BAP FISH probe is a single red and single green signal for derivative chromosomes and a single fusion signal for the normal homolog (1F/1R/1G). However, because of the complexity of genomic changes that can occur in cancer, signal patterns other than 1F/1R/1G, that is, atypical or unusual signal patterns, are also observed [5]. We describe the validation of a locus specific identifier (LSI)-BCL6 FISH assay using a digital analysis system, as well as our experience with unusual signal patterns observed using this assay. We demonstrate that unusual FISH signal patterns can be associated with copy number alterations in addition to rearrangements involving the BCL6 locus at 3q27 KCI Citation Count: 0