Design and Validation of a Custom Next-Generation Sequencing Panel in Pediatric Acute Lymphoblastic Leukemia

The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-target...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-02, Vol.24 (5), p.4440
Main Authors: Gil, José Vicente, Such, Esperanza, Sargas, Claudia, Simarro, Javier, Miralles, Alberto, Pérez, Gema, de Juan, Inmaculada, Palanca, Sarai, Avetisyan, Gayane, Santiago, Marta, Fuentes, Carolina, Fernández, José María, Vicente, Ana Isabel, Romero, Samuel, Llop, Marta, Barragán, Eva
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Acute lymphocytic leukemia
Cell cycle
Child
childhood acute lymphoblastic leukemia
Children
Copy number
Cytogenetics
DNA Copy Number Variations
Gene expression
Gene frequency
Genes
Health aspects
High-Throughput Nucleotide Sequencing
Humans
INDEL Mutation
Leukemia
Lymphatic leukemia
Medical laboratories
molecular characterization
Mutation
Next-generation sequencing
NGS
Nucleotides
Patients
Pediatrics
Polymorphism, Single Nucleotide
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Reproducibility
Scientific equipment and supplies industry
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Description
Summary:The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-targeted panels are able to capture the most relevant alterations in a cost-effective and fast way. However, comprehensive ALL panels assessing all relevant alterations are scarce. Here, we design and validate an NGS panel including single-nucleotide variants (SNVs), insertion-deletions (indels), copy number variations (CNVs), fusions, and gene expression (ALLseq). ALLseq sequencing metrics were acceptable for clinical use and showed 100% sensitivity and specificity for virtually all types of alterations. The limit of detection was established at a 2% variant allele frequency for SNVs and indels, and at a 0.5 copy number ratio for CNVs. Overall, ALLseq is able to provide clinically relevant information to more than 83% of pediatric patients, making it an attractive tool for the molecular characterization of ALL in clinical settings.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24054440