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 1.0Mb 3' of MYC.