Het aandeel van genetische predispositie als oorzaak voor kinderkanker: een geïntegreerde aanpak van uitgebreide fenotypering en state-of-the-arts genotypering

Rationale: Recognition of genetic predisposition in children with cancer or neoplasms is of high clinical significance since it might influence therapy choices, surveillance policies and counseling of relatives. Cancer predisposition syndromes (CPSs) can be suspected based on specific hallmarks such as a positive family history or the presence of congenital anomalies. Due to the expanding phenotypic diversity, the upfront ‘phenotype based’ recognition of CPSs is becoming more challenging for clinicians. Furthermore, next-generation sequencing (NGS) studies have revealed mutations in pediatric cancer predisposition genes in patients without any clinical features suggestive for genetic predisposition. Objective: To evaluate the performance of a ‘genotype first approach’ (WES-based panel analysis) in diagnostics of genetic predisposition in children with cancer or neoplasms, compared to the current ‘phenotype first approach’ (standard of care). In particular we will focus on discrepancies in CPS diagnoses between these two approaches. Study design: Prospective nationwide cohort study. We will use WES-data generated routinely from all children diagnosed with cancer or neoplasms in the Princess Máxima Center. After informed consent, a panel of known pediatric cancer predisposing genes will be analysed in the germline data. Study population: A prospective cohort of children (age < 19 years) who are newly diagnosed with and/or treated for cancer or neoplasms at the Princess Máxima Center in a period of three years. Main study parameters/endpoints: Pediatric cancer predisposition syndromes diagnoses (molecular and/or clinical). We will compare the number of cancer predisposition syndromes diagnosed by the genotype first approach (molecular diagnosis based on WES panel analysis) to the phenotype first approach (clinical diagnosis and/or molecular diagnosis based on targeted tests).

There might be discrepancies in number and type of Cancer Predisposition Syndrome diagnoses between the genotype first and the phenotype first approach.

Not applicable

None