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Abstract
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 datasets.
Results
In total, 1/3rd of patients had a clinical indication for genetic testing according to current recommendations and 10.1% (n=14/139) of children harbored a cancer predisposition. Out of these, 71.4% (n=10/14) 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%. While our data revealed a high rate of genetic predisposition (40%, n=4/10) in Myelodysplastic Syndrome cases, no (likely) pathogenic variants were identified in the sarcoma and lymphoma group.
Conclusion
In summary, our data shows high checklist sensitivity, particular to identify childhood cancer predisposition syndromes. Nevertheless, the here employed checklist 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.
Keywords
Article info
Publication history
Accepted:
April 27,
2023
Received in revised form:
April 25,
2023
Received:
November 18,
2022
Publication stage
In Press Accepted ManuscriptIdentification
Copyright
© 2023 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.
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