The genetics of Hodgkin lymphoma: an overview and clinical implications

The goal of this review is to give an overview of the genetics of classical Hodgkin lymphoma. Copy number changes, somatic mutations, genome-wide association studies, changes in gene expression, familial classical Hodgkin lymphoma and epigenetic changes will be reviewed. In doing so, special focus is placed on the way recent discoveries have influenced clinical research, diagnostics, treatment and remission monitoring. Furthermore, emphasis is put on how these advances can help to advance the treatment of elderly patients who have a markedly worse prognosis than younger patients.

Frequent amplifications of the 9p24.1 locus in classical Hodgkin lymphoma could be the basis for the success of immune checkpoint inhibitors targeting PD-1 or PD-L1 in this disease. The same amplification also affects the JAK/STAT pathway, which has also been targeted in recent clinical trials. Hodgkin lymphoma-specific copy number alterations and mutations have recently been found to be detectable in cell-free DNA. This could provide the basis for advances in the detection of residual disease during treatment and while monitoring patients in remission.

The advent of new technologies such as massive parallel sequencing has improved our understanding of the genetics of classical Hodgkin lymphoma. Some of these discoveries are now being translated into clinical research in the form of new diagnostics and treatments.