Introduction
Unlike adult cancer, which is more commonly secondary to aging, environmental exposures and lifestyle habits, childhood cancer is remarkably different. No prominent causative factors have been identified except for rare cases involving cancers attributed to viral infections, radiation, oncological and immunosuppressive therapy. Recent studies have identified a cancer predisposition syndrome (CPS) in 10% of children with cancer1-5. The frequency of germline variants is different between tumor types but appears to be more significant in some malignancies such as central nervous system tumors and paraganglioma6,7.
In routine pediatric oncology practice, detecting these syndromes can be challenging. There is a paucity of information regarding which patients should be studied, when screening should be performed (e.g., at diagnosis, at the end of the treatment), and which specific test should be done, if whole exome sequencing (WES), trio-whole exome sequencing or gene panels8. Moreover, interpreting the genomic results (based on established criteria9) can be overwhelming for clinicians.
Recent publications have reviewed the importance of early recognition of these syndromes10-12 and clinical screening tools have been proposed to help identify the patients who carry higher risk. Particularly useful are the classic Jongmans criteria13 and the recent McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG)14-16.
Genetic studies may not be universally accessible within all healthcare systems. Consequently, it is crucial to prioritize the selection of patients eligible for such studies. Heterogeneous strategies are observed in various institutions, achieving similar outcomes17-23.
There has yet to be a consensus on the best time to carry out the genetic study, whether at diagnosis, in the middle of, or at the end of treatment. The most crucial advantage of performing the CPS study at diagnosis is adjusting the patient’s treatment to perform personalized medicine. Avoiding radiotherapy in particularly sensitive patients (e.g., Li Fraumenni patients24,25), or choosing targeted therapy specific to the patient’s syndrome (e.g. immunotherapy in patients with constitutional mismatch repair deficiency26), are some advantages of performing this study early. Nevertheless, delaying the family cancer appointment could provide an opportunity for more comprehensive information on treatment-related toxicity and family medical history.
There is no consensus on which genetic study to perform, whether a WES or a gene-targeted panel focusing on known genes associated with CPS8. Before the application of next-generation sequencing (NGS), single-gene analysis of specific high-risk genes was performed, a time-consuming and expensive approach. The widespread availability and implementation of NGS significantly enhance the efficiency of identifying individuals with CPS.
We present our experience in the recent years detecting patients with CPS by multigene panel analysis. We highlight the importance of dedicating a specific appointment with families to obtain a thorough and accurate clinical history and to increase the efficiency of the process.