title: DNA repair: the link between primary immunodeficiency and cancer.
abstract: The adaptive component of the immune system depends greatly on the generation of genetic diversity provided by lymphocyte-specific genomic rearrangements. V(D)J recombination, class switch recombination (CSR), and somatic hypermutation (SHM) constitute complex and vulnerable processes that are orchestrated by a multitude of DNA repair pathways. When inherited defects in certain DNA repair proteins are present, lymphocyte development can be compromised and, consequently, patients can develop primary immunodeficiencies (PIDs). PID patients often have a strong predisposition for cancer development as a result of genomic instability generated from defective DNA repair mechanisms. Tumors of lymphoid origin are one of the most common PID-associated cancers, likely due to DNA lesions resulting from defective V(D)J, CSR, and SHM. In this review, we describe PID syndromes that confer an increased risk for cancer development. Furthermore, we discuss the role of the affected proteins in tumorigenesis/lymphomagenesis.
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Noel Fcc
authors.initials: NF
authors.lastname: de Miranda
authors.forename: Andrea
authors.initials: A
authors.lastname: Björkman
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pan-Hammarström
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000378:metabolism*; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics; D004260:DNA Repair; D006801:Humans; D017578:Immunoglobulin Class Switching; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology*; D049932:Nijmegen Breakage Syndrome / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin; D060152:V(D)J Recombination / Q000235:genetics
chemical_list: D004247:DNA; D011088:DNA Ligases; D000072481:DNA Ligase ATP