Lymphoma genetics
Genetics plays a crucial role in the classification and treatment of non-Hodgkin lymphoma. Various techniques, including conventional cytogenetics, fluorescence in-situ hybridization, and next-generation sequencing, have significantly contributed to our understanding of the chromosomal abnormalities, driver mutations, and gene expression profiles associated with different types of B-cell lymphomas. For example, Burkitt lymphoma, characterized by chromosomal rearrangements involving the proto-oncogene MYC , can now be further categorized based on mutational profiling patterns. Diffuse large B-cell lymphoma, traditionally classified into germinal center and activated B-cell types based on gene expression, is now better defined and subclassified through genomic signatures. Mantle cell lymphoma, resulting from rearrangements involving cyclin proto-oncogenes, can be prognosticated by assessing TP53 mutation status. Follicular lymphoma, often linked to the IGH::BCL2 translocation, incorporates genetic data (m7-FLIPI score) for prognostic purposes. Lymphoplasmacytic lymphoma, driven by the MYD88 L265P mutation, is influenced by CXCR4 mutation status when determining prognosis. Moreover, chronic lymphocytic leukemia/small lymphocytic lymphoma requires genetic characterization, including chromosomal gains/deletions, TP53 mutations, and immunoglobulin heavy chain gene variable somatic hypermutation status, to determine prognosis and guide treatment. Furthermore, our molecular understanding of T-cell lymphomas has also advanced. Anaplastic large-cell lymphoma is divided into two types based on the presence of anaplastic lymphoma kinase (ALK) rearrangements, with ALK-negative cases impacted by the rearrangement patterns of other genes. Nodal T-follicular helper lymphomas exhibit distinct mutational patterns, and improved comprehension of peripheral T-cell lymphomas, not otherwise specified, involves analyzing GATA3 and TBX1 transcriptional patterns. This review provides an up-to-date overview of the most significant genetic and molecular alterations associated with a subset of non-Hodgkin lymphomas.
