Publication:
Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

Simple item page
dc.affiliation.dptoUC3M. Departamento de Informáticaes
dc.affiliation.grupoinvUC3M. Grupo de Investigación: Laboratorio de Control, Aprendizaje y Optimización de Sistemas (CAOS)es
dc.contributor.authorSanchez, Ricardo
dc.contributor.authorDorado Alfaro, Sara
dc.contributor.authorToledo Heras, María Paula de
dc.date.accessioned2023-04-24T11:12:58Z
dc.date.available2023-04-24T11:12:58Z
dc.date.issued2022-07-29
dc.descriptionDocumento escrito por un elevado número de autores/as, solo se referencia el/la que aparece en primer lugar y los/as autores/as pertenecientes a la UC3M.es
dc.description.abstractThe screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E−4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.en
dc.description.sponsorshipThis project was funded in part by CRIS CANCER FOUNDATIONen
dc.format.extent11
dc.identifier.bibliographicCitationSánchez, R., et al.(2022). Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA. Scientific Reports, 12, 13057.en
dc.identifier.doihttps://doi.org/10.1038/s41598-022-17271-3
dc.identifier.issn2045-2322
dc.identifier.publicationfirstpage1
dc.identifier.publicationissue13057
dc.identifier.publicationlastpage11
dc.identifier.publicationtitleScientific Reportsen
dc.identifier.publicationvolume12
dc.identifier.urihttps://hdl.handle.net/10016/37183
dc.identifier.uxxiAR/0000032302
dc.language.isoeng
dc.publisherNature Researchen
dc.rights© The Author(s) 2022.en
dc.rightsAtribución 3.0 España*
dc.rights.accessRightsopen accessen
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subject.ecienciaBiología y Biomedicinaes
dc.subject.ecienciaInformáticaes
dc.subject.ecienciaMedicinaes
dc.subject.otherCanceres
dc.subject.otherMolecular Medicinees
dc.titleDetection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNAen
dc.typeresearch article*
dc.type.hasVersionVoR*
dspace.entity.typePublication
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Detection_SR_2022.pdf
Size:
2.46 MB
Format:
Adobe Portable Document Format
Download
Collections
DI - CAOS - Artículos de Revistas