MYC gene and its abnormalities with a focus on aggressive B-cell lymphomas

Abstract

The MYC gene encodes the Myc protein, which is one of the most important transcription factors regulating a wide range of cellular functions, including cell proliferation, differentiation and apoptosis. Deregulation of the MYC gene occurs at various levels and its increased expression is associated with a variety of cancers. Deregulation of the gene through chromosomal rearrangement is typical for B-cell lymphomas and is usually accompanied by a more aggressive nature of the disease with an unfavourable prognosis. B-cell lymphomas with a proven MYC gene rearrangement show high variability in the localization of breakpoints in the 8q24 region. The rearrangement involves various translocation partners, both immunoglobulin (IG) genes and non-immunoglobulin (non-IG) genes. The involvement of IG genes as translocation partners of MYC is considered a negative prognostic factor. Co-occurring aberrations of other oncogenes have a significant impact on the prognosis of patients with MYC gene rearrangements. The presence or absence of MYC, BCL2 and BCL6 gene rearrangements, together with morphological assessment, is the defining criterion for the classification of aggressive B-cell lymphomas according to the 5th revised WHO classification (2022). The most suitable method for detecting rearrangements is fluorescence in situ hybridization (FISH), which can be used both on native material and on tissue sections from paraffin blocks. This review discusses the physiological function of the MYC gene, its deregulation, types of chromosomal aberrations involving MYC gene and their role in cancer pathogenesis with a focus on B-cell lymphomas.