MYC Breakapart Probe

Translocations involving the MYC oncogene (Avian Myelocytomatosis Viral Oncogene Homologue) are similar in B-ALL as they are in Burkitt’s Lymphoma and result in the close juxtaposition of MYC to IGH, IGL and IGK in t(8;14) , t(8;22) and t(2;8) respectively. In each case this results in deregulation of the MYC as a result of being close to the constitutively active Immunoglobulin locus, increased transcription and neoplastic growth. The breakpoints involved are widely scattered throughout the gene but the t(8;14) translocation always spares the protein coding exons which become attached to the derived 14, whilst in the t(2;8) and t(8;22) the MYC remains on the chromosome 8 and the Immunoglobulin locus joins it, resulting in the close positioning of the MYC and Immunoglobulin locus. ALL with these associated translocations (less than 5% of all ALLs) are invariably of the L3 subtype, most are caused by the t(8;14) (85%), t(8;22) is the next most common at 10% and finally t(2;8) makes up the remaining 5%. Patients with MYC rearrangements were originally thought to have poor prognoses but they do respond well to intensive chemotherapy, which affords them an increased survival rate. This shows that cytogenetic confirmation of the rearrangement is necessary to manage the patient effectively.

For the MYC fission product, the probes are spaced widely apart (717 kb) so as to be capable of picking up each of the three translocations. The proximal probe (177 kb) is 332 kb 3’ of the gene and is labelled in red, whilst the distal probe (188 kb) is 380 kb 5’ of the gene and is labelled in green.