The BCL6 FISH probe set is designed to detect rearrangements involving regions of the human BCL6 gene located on chromosome band 3q27. The kit contains two differentially labeled Locus Specific Probes (LSP), one covering a genomic area upstream of the 5’ (start) end of the BCL6 gene, the other matching the BCL6 gene itself along with some untranslated sequences downstream of the 3’ (end) part of the gene. The two probes are designed to recognize sequences on both sides of an area in front of the BCL6 gene where breakpoints are frequently found. In addition to revealing breaks, which lead to translocation of parts or all of the gene or its fusion to other genes, the probe set can also be used to identify other BCL6 aberrations such as deletions, amplifications or chromosome 3 hyperdiploidy. 

BCL6 Gene

Fluorescence in situ hybridization (FISH) is a powerful technique developed to detect presence or absence, location, integrity and amount of genomic sequences in tissue samples or cells.^1-3

Members of the BCL2 family of proteins play important roles in the control of programmed cell death (apoptosis). They comprise proteins that facilitate apoptosis as well as apoptosis inhibitors.⁴ At least some family members are believed to elicit release of cytochrome C from mitochondria and subsequent cell death. In addition, some members are involved in the activation of members of the caspase family of apoptosis enzymes.

One family member, B-Cell Lymphoma 6 (BCL6), is a conserved zink finger-type transcription factor that can bind to specific DNA sequences and inhibit transcription. Also known as Lymphoma Associated Zinc finger on chromosome 3 or Zinc Finger Protein 51, it can recruit other transcription factors and corepressors to its binding site. One important hematopoietic signal transduction pathway that has been shown to be regulated by BCL6-mediated transcriptional modulation are the STAT-dependent B cell responses to interleukin 4 (IL-4).^5,6

BCL6 is a protein predominantly expressed in germinal center B and T cells and various lymphoid tissues but has also been found in other cell types such as skeletal muscle cells and keratinocytes.⁷ The protein is highly conserved throughout evolution.
 

BCL6 and Lymphoma

Lymphomas are malignant conditions of the lymphatic part of the circulatory system. They are the most common blood cancer in the developed world. They also are among the small number of cancer types that has seen significant decreases in mortality in recent years, in large part owing to earlier diagnosis resulting from molecular and cytogenetic characterization.⁸

Traditionally, there are two main categories of lymphoma. One is Hodgkins lymphoma, a relatively rare malignancy of a specific B cell type. The other type, Non-Hodgkin-Lymphoma, is a heterogenous group comprising all other forms of the disease, of which more than 60 have been described.

Aberrations of the BCL6 gene are abundant in a number of lymphoma types but are most commonly detected in Diffuse Large B-cell Lymphoma (DLBCL, the most common non-Hodgkin lymphoma) and frequently also found in Follicular Lymphoma (FL) and in a significant number of cases of Hodgkin lymphoma.^9-11Low expression of BCL6 has been associated with poor clinical prognosis, whereas high expression of BCL6 is generally considered a sign of better clinical outcome.^12,13 Recently, BCL6 has also been recognized as a theranostic marker enabling acute lymphoblastic leukemia cells to survive kinase inhibitor treatment.^14,15

A large number of different translocations involving the BCL6 gene has been described in lymphomas. About half of the known rearrangements involve immunoglobulin genes as the other partner, but a variety of other genes, located on several different chromosomes, has been observed fused to BCL6 as well. In total, more than 30 partner genes have been found fused with BCL6.¹⁶

BCL6 protein can be measured by immunohistochemistry, and some gene defects can be revealed by PCR or sequencing. However, because the known translocations breakpoints are spread over a relatively large genomic region, and because a large number of different genes can serve as potential translocation partners, FISH detection using breakpoint-flanking probe pairs provides a more definitive and straightforward method of detecting rearrangements involving the BCL6 gene.
 

References

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16) http://atlasgeneticsoncology.org//Genes/BCL6ID20.html