Abstract
Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited disorders affecting one or multiple components of the innate and/or adaptive immune system. Currently, over 300 underlying genetic defects have been discovered. The most common clinical findings in patients with PIDs are infections, autoimmunity, and malignancies. Despite international efforts, the cancer risk associated with PIDs, given the heterogeneous character of this group of diseases, is difficult to estimate. The diverse underlying mechanisms of cancer in PID add another layer of complexity. Treatment of cancer within a context of PID is complicated by serious toxicities and long-term effects, including second malignancies. This review will focus on the little-known crossroad between PID and cancer genes and the value thereof for directing future research on our understanding of cancer in PID and for the identification of early cancer biomarkers in PID patients.
Highlights
Integrity of the immune system is crucial in the defense toward infectious organisms and surveillance on deviating cellular transformations, i.e., development of cancer
As “common variable immunodeficiency” (CVID) is the most common Primary immunodeficiency diseases (PIDs) subtype, incidence results are often focused on this subgroup, revealing a higher incidence for lymphoma and an association with stomach and skin cancer
We provide a synopsis on the current knowledge about the genetics of malignancies in PID
Summary
Integrity of the immune system is crucial in the defense toward infectious organisms and surveillance on deviating cellular transformations, i.e., development of cancer. Germline mutations in JAK-STAT signaling are associated with PIDs. Notably, the PID phenotypes depend on the affected gene and mutation, ranging from mild phenotypes involving TYK2, a moderate hyper-IgE syndrome for STAT3 and severe combined immunodeficiency (SCID) in case of JAK3 mutations [41]. The PID phenotypes depend on the affected gene and mutation, ranging from mild phenotypes involving TYK2, a moderate hyper-IgE syndrome for STAT3 and severe combined immunodeficiency (SCID) in case of JAK3 mutations [41] It is only recently, that mutations in TYK2, a JAK kinase family member, were found in the germline of patients presenting with a second primary leukemia, causing constitutive JAK signaling and a propensity for developing leukemia [42]. The high level of intersection might partially result from the observation that hypermutation is especially found in brain tumors, the H3.3 or H3.1 K27-wildtype high-grade gliomas with biallelic germline mutations in MSH6 or PMS2 [52]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
