Genomics Driving Diagnosis and Treatment of Inborn Errors of Immunity With Cancer Predisposition
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, přehledy, práce podpořená grantem, Research Support, N.I.H., Extramural
PubMed
35364342
DOI
10.1016/j.jaip.2022.03.012
PII: S2213-2198(22)00290-2
Knihovny.cz E-zdroje
- Klíčová slova
- Autoimmune lymphoproliferative syndrome, Cancer predisposition, DNA repair defect, Defect in cell intrinsic immunity, EBV susceptibility, Genomics, Germline genetic variant, Inborn error of immunity, Oncogene, Regulatory T-cell disorder, Small molecular compound, Somatic genetic variant,
- MeSH
- genetická predispozice k nemoci MeSH
- genomika MeSH
- infekce virem Epsteina-Barrové * MeSH
- lidé MeSH
- nádory * diagnóza genetika terapie MeSH
- virus Epsteinův-Barrové MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
Inborn errors of immunity (IEI) are genetically and clinically heterogeneous disorders that, in addition to infection susceptibility and immune dysregulation, can have an enhanced cancer predisposition. The increasing availability of upfront next-generation sequencing diagnostics in immunology and oncology have uncovered substantial overlap of germline and somatic genetic conditions that can result in immunodeficiency and cancer. However, broad application of unbiased genetics in these neighboring disciplines still needs to be deployed, and joined therapeutic strategies guided by germline and somatic genetic risk factors are lacking. We illustrate the current difficulties encountered in clinical practice, summarize the historical development of pathophysiological concepts of cancer predisposition, and review select genetic, molecular, and cellular mechanisms of well-defined and illustrative disease entities such as DNA repair defects, combined immunodeficiencies with Epstein-Barr virus susceptibility, autoimmune lymphoproliferative syndromes, regulatory T-cell disorders, and defects in cell intrinsic immunity. We review genetic variants that, when present in the germline, cause IEI with cancer predisposition but, when arising as somatic variants, behave as oncogenes and cause specific cancer entities. We finally give examples of small molecular compounds that are developed and studied to target genetically defined cancers but might also proof useful to treat IEI.
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