Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients
Por:
Montaño A, Hernández-Sánchez J, Forero-Castro M, Matorra-Miguel M, Lumbreras E, Miguel C, Santos S, Ramírez-Maldonado V, Fuster JL, de Las Heras N, García-de Coca A, Sierra M, Dávila J, de la Fuente I, Olivier C, Olazabal J, Martínez J, Vega-García N, González T, Hernández-Rivas JM and Benito R
Publicada:
1 sep 2020
Ahead of Print:
21 sep 2020
Categoría:
Medicine (miscellaneous)
Resumen:
Background: B-acute lymphoblastic leukemia (B-ALL) is a hematological neoplasm of the stem lymphoid cell of the B lineage, characterized by the presence of genetic alterations closely related to the course of the disease. The number of alterations identified in these patients grows as studies of the disease progress, but in clinical practice, the conventional techniques frequently used are only capable of detecting the most common alterations. However, techniques, such as next-generation sequencing (NGS), are being implemented to detect a wide spectrum of new alterations that also include point mutations. Methods: In this study, we designed and validated a comprehensive custom NGS panel to detect the main genetic alterations present in the disease in a single step. For this purpose, 75 B-ALL diagnosis samples from patients previously characterized by standard-of-care diagnostic techniques were sequenced. Results: The use of the custom NGS panel allowed the correct detection of the main genetic alterations present in B-ALL patients, including the presence of an aneuploid clone in 14 of the samples and some of the recurrent fusion genes in 35 of the samples. The panel was also able to successfully detect a number of secondary alterations, such as single nucleotide variants (SNVs) and copy number variations (CNVs) in 66 and 46 of the samples analyzed, respectively, allowing for further refinement of the stratification of patients. The custom NGS panel could also detect alterations with a high level of sensitivity and reproducibility when the findings obtained by NGS were compared with those obtained from other conventional techniques. Conclusions: The use of this custom NGS panel allows us to quickly and efficiently detect the main genetic alterations present in B-ALL patients in a single assay (SNVs and insertions/deletions (INDELs), recurrent fusion genes, CNVs, aneuploidies, and single nucleotide polymorphisms (SNPs) associated with pharmacogenetics). The application of this panel would thus allow us to speed up and simplify the molecular diagnosis of patients, helping patient stratification and management.
Filiaciones:
Montaño A:
IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigación del Cáncer (CIC), 37007 Salamanca, Spain
Hernández-Sánchez J:
IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigación del Cáncer (CIC), 37007 Salamanca, Spain
Forero-Castro M:
Escuela de Ciencias Biológicas (Grupo de investigación GICBUPTC), Universidad Pedagógica y Tecnológica de Colombia, Tunja 150003, Colombia
Matorra-Miguel M:
IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigación del Cáncer (CIC), 37007 Salamanca, Spain
Lumbreras E:
IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigación del Cáncer (CIC), 37007 Salamanca, Spain
Miguel C:
IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigación del Cáncer (CIC), 37007 Salamanca, Spain
Santos S:
IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigación del Cáncer (CIC), 37007 Salamanca, Spain
Ramírez-Maldonado V:
IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigación del Cáncer (CIC), 37007 Salamanca, Spain
Fuster JL:
Sección de Oncohematología Pediátrica, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB), 30120 Murcia, Spain
de Las Heras N:
Departamento de Hematología-Hospital Virgen Blanca, 24008 León, Spain
García-de Coca A:
Departamento de Hematología-Hospital Clínico de Valladolid, 47003 Valladolid, Spain
Sierra M:
Complejo Sanitario de Zamora, 49022 Zamora, Spain
Dávila J:
Departamento de Hematología-Hospital Universitario de Salamanca, 37007 Salamanca, Spain
de la Fuente I:
Departamento de Hematología-Hospital Rio Hortega, 47012 Valladolid, Spain
Olivier C:
Servicio de Hematología y Hemoterapia-Complejo Sanitario de Segovia, 40002 Segovia, Spain
Olazabal J:
Departamento de Hematología-Hospital Universitario de Burgos, 09006 Burgos, Spain
Martínez J:
Departamento de Hematología-Hospital Universitario 12 de Octubre, 28041 Madrid, Spain
Vega-García N:
Laboratorio de Hematología, Instituto de Investigación, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
González T:
Departamento de Hematología-Hospital Universitario de Salamanca, 37007 Salamanca, Spain
Hernández-Rivas JM:
IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigación del Cáncer (CIC), 37007 Salamanca, Spain
Departamento de Hematología-Hospital Universitario de Salamanca, 37007 Salamanca, Spain
Benito R:
IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigación del Cáncer (CIC), 37007 Salamanca, Spain
Green Published, gold
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