PURPOSE: Clinical checklists are the standard of care to determine whether a child with cancer shows indications for genetic testing. Nevertheless, the efficacy of these tests to reliably detect genetic cancer predisposition in children with cancer is still insufficiently investigated.
METHODS: We assessed the validity of clinically recognizable signs to identify cancer predisposition by correlating a state-of-the-art clinical checklist to the corresponding exome sequencing analysis in an unselected single-center cohort of 139 child-parent data sets.
RESULTS: In total, one-third of patients had a clinical indication for genetic testing according to current recommendations, and 10.1% (14 of 139) of children harbored a cancer predisposition. Of these, 71.4% (10 of 14) were identified through the clinical checklist. In addition, >2 clinical findings in the checklist increased the likelihood to identifying genetic predisposition from 12.5% to 50%. Furthermore, our data revealed a high rate of genetic predisposition (40%, 4 of 10) in myelodysplastic syndrome cases, while no (likely) pathogenic variants were identified in the sarcoma and lymphoma group.
CONCLUSION: In summary, our data show high checklist sensitivity, particularly in identifying childhood cancer predisposition syndromes. Nevertheless, the checklist used here also missed 29% of children with a cancer predisposition, highlighting the drawbacks of sole clinical evaluation and underlining the need for routine germline sequencing in pediatric oncology.
|Fachzeitschrift||Genetics in Medicine|
|Publikationsstatus||Veröffentlicht - Aug. 2023|
DFG-Fachsystematik nach Fachkollegium
Ziele für nachhaltige Entwicklung
ASJC Scopus Sachgebiete
- Humans, Child, Genetic Predisposition to Disease, Early Detection of Cancer, Neoplasms/diagnosis, Genetic Testing, Genotype, Neoplastic Syndromes, Hereditary/diagnosis, Germ-Line Mutation/genetics, Clinical checklists, Pediatric cancer, Germline cancer predisposition, Trio sequencing, Genetic testing