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.