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Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia

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Specialty Biology
Date 2022 Apr 25
PMID 35463953
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Abstract

Development of next-generation sequencing (NGS) has provided useful genetic information to redefine diagnostic, prognostic, and therapeutic strategies for the management of acute leukemia (AL). However, the application in the clinical setting is still challenging. Our aim was to validate the AmpliSeq™ for Illumina® Childhood Cancer Panel, a pediatric pan-cancer targeted NGS panel that includes the most common genes associated with childhood cancer, and assess its utility in the daily routine of AL diagnostics. In terms of sequencing metrics, the assay reached all the expected values. We obtained a mean read depth greater than 1000×. The panel demonstrated a high sensitivity for DNA (98.5% for variants with 5% variant allele frequency (VAF)) and RNA (94.4%), 100% of specificity and reproducibility for DNA and 89% of reproducibility for RNA. Regarding clinical utility, 49% of mutations and 97% of the fusions identified were demonstrated to have clinical impact. Forty-one percent of mutations refined diagnosis, while 49% of them were considered targetable. Regarding RNA, fusion genes were more clinically impactful in terms of refining diagnostic (97%). Overall, the panel found clinically relevant results in the 43% of patients tested in this cohort. To sum up, we validated a reliable and reproducible method to refine pediatric AL diagnosis, prognosis, and treatment, and demonstrated the feasibility of incorporating a targeted NGS panel into pediatric hematology practice.

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References
1.
Inaba H, Mullighan C . Pediatric acute lymphoblastic leukemia. Haematologica. 2020; 105(11):2524-2539. PMC: 7604619. DOI: 10.3324/haematol.2020.247031. View

2.
Wang R, Chen C, Jing Y, Qin J, Li Y, Chen G . Characteristics and prognostic significance of genetic mutations in acute myeloid leukemia based on a targeted next-generation sequencing technique. Cancer Med. 2020; 9(22):8457-8467. PMC: 7666719. DOI: 10.1002/cam4.3467. View

3.
Manara E, Bisio V, Masetti R, Beqiri V, Rondelli R, Menna G . Core-binding factor acute myeloid leukemia in pediatric patients enrolled in the AIEOP AML 2002/01 trial: screening and prognostic impact of c-KIT mutations. Leukemia. 2013; 28(5):1132-4. DOI: 10.1038/leu.2013.339. View

4.
Bloom M, Maciaszek J, Clark M, Pui C, Nichols K . Recent advances in genetic predisposition to pediatric acute lymphoblastic leukemia. Expert Rev Hematol. 2019; 13(1):55-70. PMC: 10576863. DOI: 10.1080/17474086.2020.1685866. View

5.
Neumann M, Vosberg S, Schlee C, Heesch S, Schwartz S, Gokbuget N . Mutational spectrum of adult T-ALL. Oncotarget. 2015; 6(5):2754-66. PMC: 4413615. DOI: 10.18632/oncotarget.2218. View