Genetic Disorders with Predisposition to Paediatric Haematopoietic Malignancies—A Review

SIMPLE SUMMARY: A significant progress in understanding the genetic basis of childhood cancers has been made over the past years. Genome sequencing has identified significant differences between paediatric and adult cancers. A higher prevalence of germline alterations in cancer predisposition genes is observed, in comparison to somatic mutations in paediatric cancers. Interestingly, pathogenic germline variants and somatic mutations can affect the same genes. The early recognition of genetic predispositions for childhood cancers may provide an opportunity of therapy adjustment and specific screening for different syndrome-related malignancies. Research on the biological function of gene variants with increased cancer predispositions is critical to the needs of adequate patient management. Genetic counselling with targeted therapy have become basis of integrated cancer care in paediatric oncology. ABSTRACT: The view of paediatric cancer as a genetic disease arises as genetic research develops. Germline mutations in cancer predisposition genes have been identified in about 10% of children. Paediatric cancers are characterized by heterogeneity in the types of genetic alterations that drive tumourigenesis. Interactions between germline and somatic mutations are a key determinant of cancer development. In 40% of patients, the family history does not predict the presence of inherited cancer predisposition syndromes and many cases go undetected. Paediatricians should be aware of specific symptoms, which highlight the need of evaluation for cancer syndromes. The quickest possible identification of such syndromes is of key importance, due to the possibility of early detection of neoplasms, followed by presymptomatic genetic testing of relatives, implementation of appropriate clinical procedures (e.g., avoiding radiotherapy), prophylactic surgical resection of organs at risk, or searching for donors of hematopoietic stem cells. Targetable driver mutations and corresponding signalling pathways provide a novel precision medicine strategy.Therefore, there is a need for multi-disciplinary cooperation between a paediatrician, an oncologist, a geneticist, and a psychologist during the surveillance of families with an increased cancer risk. This review aimed to emphasize the role of cancer-predisposition gene diagnostics in the genetic surveillance and medical care in paediatric oncology.