Identification of genetic variants related to cancer predisposition in cohort of patients with embryonal tumors or pediatric tumors and additional clinical signs

Abstract

Pediatric tumors are intrinsically different from tumors in adults, and childhood cancer is inseparable from processes of cell differentiation and organogenesis. The causes of most pediatric cancers are unknown and there is no significant association with environmental risk factors; therefore, nothing can be done for prevention. Leukemias, lymphomas and tumors of the central nervous system are the most frequent neoplasms in children, but most other solid tumors are less studied because they are rare among pediatric tumors in general. One of the great challenges of biomedical research is to associate human genetic variants with phenotypic characteristics. Rare and common genetic variations influence cancer susceptibility, not only in cancer predisposition syndromes (caused by rare mutations with high penetrance), but also in susceptibility to sporadic neoplasms (combination of low to moderate risk variants). The prevalence and the spectrum of mutated genes in the predisposition to cancer among children and adolescents remain little explored. In this context, our project aims to study the genetic variants that are associated with the development of pediatric cancer, especially in hepatoblastoma-type embryonic tumors and patients with pediatric tumors and additional clinical signs. As an approach, we will investigate copy number alterations per array-CGH and complete exome sequencing in cohort of patients affected by pediatric malignancies, aiming at the identification and characterization of the spectrum of germline genetic variants associated with predisposition to cancer.