Novel FISH probes designed to detect IGK-MYC and IGL-MYC rearrangements in B-cell lineage malignancy identify a new breakpoint cluster region designated BVR2.

Detection of translocations involving MYC at 8q24.1 in B-cell lineage malignancies (BCL) is important for diagnostic and prognostic purposes. However, routine detection of MYC translocations is often hampered by the wide variation in breakpoint location within the MYC region, particularly when a gene other than IGH, such as IGK or IGL, is involved. To address this issue, we developed and validated four fluorescence in situ hybridization (FISH) probes: two break apart probes to detect IGK and IGL translocations, and two dual-color, dual-fusion FISH (D-FISH) probes to detect IGK-MYC and IGL-MYC. MYC rearrangements (four IGK-MYC, 12 IGL-MYC and four unknown partner gene-MYC) were correctly identified in 20 of 20 archival BCL specimens known to have MYC rearrangements not involving IGH. Seven specimens, all of which lacked MYC rearrangements using a commercial IGH/MYC D-FISH probe, were found to have 8q24 breakpoints within a cluster region >350-645 kb 3' from MYC, provisionally designated as Burkitt variant rearrangement region 2 (BVR2). FISH is a useful ancillary tool in identifying MYC rearrangements. In light of the discovery of the distally located BVR2 breakpoint cluster region, it is important to use MYC FISH probes that cover a breakpoint region at least 1.0 Mb 3' of MYC.