Insights into germline predisposition to pediatric lymphoid malignancies

Hematopoietic malignancies (HM) represent the most common form of pediatric cancer with lymphoid malignancies being the predominant subtype in kids. The majority of lymphoid malignancies are proposed to occur sporadically with environmental, infectious and inflammatory triggers impacting oncogenesis in ways that are not yet fully understood. With the increased adoption of germline genetic testing in children with cancer, genetic predisposition to lymphoid malignancies is now recognized as an important aspect of clinical care and research. Pathogenic variants in genes important for lymphocyte development, including cell differentiation, DNA recombination, recognition and repair of DNA damage, apoptosis, RNA processing, and intracellular signaling all converge on an increased risk for lymphoid malignancies. Herein, we review several genetic predispositions to lymphoid malignancies with a focus on the underlying biological defect, as well as the associated oncologic and non-oncologic manifestations.