[Genetic predisposition to childhood cancer]

Abstract

Tackling the topic of genetic predisposition to childhood cancer requires close co-operation between pathologists, pediatric oncologists, and human geneticists. It is not just about the precise diagnosis and the most effective treatment of the cancer, but also to prevent further cancerous diseases for those affected and also their family members. On the basis of examples such as Li-Fraumeni syndrome, constitutional mismatch repair deficiency (CMMRD), medullo- and neuroblastoma, as well as hematological neoplasias, we will discuss the criteria for tumor predisposition genetic syndromes, the relationship between somatic and germline variants, and the immediate clinical consequences. In some cases, the diagnosis of a genetic tumor predisposition syndrome has immediate consequences for the treatment, e. g. to avoid radiotherapy for Li-Fraumeni syndrome, which would otherwise significantly increase the probability of secondary, independent tumors. Predictive diagnostics can be offered to identify the family members who carry the pathogenic variant. Because of their increased tumor risk, they should be integrated into cancer surveillance programs. Evidence-based data show that this significantly improves overall survival.

Keywords: DNA mismatch repair; Early detection of cancer; Genetic counselling; Genetic predisposition to disease; Li-Fraumeni syndrome.