11B. Germ cell tumors: optimal diagnosis and follow up based on understanding epidemiology and pathogenesis.

Malignant germ cell tumors represent 3.5% of all cancers in childhood and 14% of the neoplasms diagnosed in the 15-19 year age group. Within the pediatric age group (i.e. up to 18 years) germ cell tumors represent about 5% of all neoplasms, of which about 50% are gonadal (either testis or ovary) and 50% extragonadal. Of the latter fifty percent, 20% are intracranial and 30% extracranial germ cell tumors. In the age group till 18 years germ cell tumors represent about 40 newly diagnosed cases each year in the Netherlands. About 50% of the pediatric germ cell tumors are teratoma, and considered benign, although progression to malignancy (i.e., yolk sac tumor), may occur. In contrast, germ cell tumors of adults are the most frequent malignancy of Caucasian males in the age between 18 and 40 years of age and the second cause of death.

A retrospective and prospective database will be developed by the PhD candidate in close collaboration with the University Medical Center Utrecht, as part of the two existing Centers of Expertise, as approved by our Ministry of Health. The collected liquid biopsies will be evaluated for presence of microRNA371a-3p (Salvatori et al., Stem Cell Reports 2018; Almstrup et al., Nat Rev Urol. 2020) as well as the methylated promotor fragment of the RASSF1A gene (Lobo et al. Cancers 2021). The national pathology registry (PALGA) and the national cancer registry (IKNL) will be instrumental to collect histological samples from proven refractory disease to be evaluation regarding genomic anomalies, including the regional 3p amplification (Timmerman et al., J Clin. Oncol. 2022). The PhD candidate will be trained in development of a unique database (Castor-based), and molecular investigations related to platin-resistance, including bioinformatical approaches. The secondments will be an exciting combination of  two highly experienced clinical environments (Bratislava and Praag).