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. 2025 Mar 1;47(2):74-79.
doi: 10.1097/MPH.0000000000003000. Epub 2025 Jan 30.

The Diagnostic Yield of Panel Versus Exome Sequencing to Identify Hereditary Cancer Disorders in Pediatric Cancer

Shannon M Lozinsky  1 , Carina A Iezzi  1 , Dorota Gruber  1   2 , Kenan Onel  3 , Carolyn Fein Levy  1   2
Affiliations

The Diagnostic Yield of Panel Versus Exome Sequencing to Identify Hereditary Cancer Disorders in Pediatric Cancer

Shannon M Lozinsky et al. J Pediatr Hematol Oncol. .

Abstract

This study aimed to assess whether targeted exome sequencing (TES) outperforms next- generation sequencing (NGS) panels in detecting clinically actionable cancer predisposition syndromes (CPS) in pediatric cancer patients. Patients with cancer underwent genetic counseling and NGS panel testing (27 or 64 genes). Simultaneously, a 616-gene targeted exome, including the NGS panel genes and 552 additional potential cancer-related genes, was conducted on the patients and their parents. Of 42 patients undergoing both tests, NGS panels identified an APC risk allele (RA) in a patient with ganglioglioma and a pathogenic RB1 variant in a patient with retinoblastoma. In addition to the variants found by NGS panels, TES detected a pathogenic MUTYH variant in a patient with acute lymphoblastic leukemia (ALL) and a likely pathogenic (LP) BLM variant in another patient with ALL. TES also revealed a variant in candidate CPS genes, MC1R (RA) and EXT2 (LP), in a patient with embryonal rhabdomyosarcoma and Ewing sarcoma, respectively. Despite identifying variants in candidate CPS genes ( MC1R , EXT2 ) not included on common NGS panels and known CPS genes ( MUTYH , BLM ) absent from this study's panels, the diagnostic yield of clinically actionable CPS variants did not substantially increase with TES compared with standard NGS panels in pediatric cancer patients. In conclusion, for most cases, panel testing remains appropriate for CPS diagnosis in pediatric cancer within typical clinical settings.

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Conflict of interest statement

C.F.L. owns stock in Pfizer. The remaining authors declare no conflict of interest.

References

    1. Bertacca I, Pegoraro F, Tondo A, et al. Targeted treatment of solid tumors in pediatric precision oncology. Front Oncol. 2023;13:1176790.
    1. Deyell RJ, Shen Y, Titmuss E, et al. Whole genome and transcriptome integrated analyses guide clinical care of pediatric poor prognosis cancers. Nat Commun. 2024;15:4165.
    1. Langenberg KPS, Looze EJ, Molenaar JJ. The landscape of pediatric precision oncology: program design, actionable alterations, and clinical trial development. Cancers. 2021;13:4324.
    1. Sweet-Cordero EA, Biegel JA. The genomic landscape of pediatric cancers: implications for diagnosis and treatment. Science (New York, NY). 2019;363:1170–1175.
    1. Desrosiers-Battu LR, Wang T, Reuther J, et al. Comparing the diagnostic yield of germline exome versus panel sequencing in the diverse population of the Texas KidsCanSeq Pediatric Cancer Study. JCO Precis Oncol. 2024;8:e2400187.

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