Whole genome sequencing provides comprehensive genetic testing in childhood B-cell acute lymphoblastic leukaemia.

Autor: Ryan SL; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle upon Tyne, UK., Peden JF; Illumina Cambridge Ltd., Granta Park, Great Abington, Cambridge, UK., Kingsbury Z; Illumina Cambridge Ltd., Granta Park, Great Abington, Cambridge, UK., Schwab CJ; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle upon Tyne, UK., James T; Illumina Cambridge Ltd., Granta Park, Great Abington, Cambridge, UK., Polonen P; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Mijuskovic M; Illumina Cambridge Ltd., Granta Park, Great Abington, Cambridge, UK., Becq J; Illumina Cambridge Ltd., Granta Park, Great Abington, Cambridge, UK., Yim R; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle upon Tyne, UK., Cranston RE; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle upon Tyne, UK., Hedges DJ; Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, USA., Roberts KG; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Mullighan CG; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Vora A; Department of Haematology, Great Ormond Street Hospital, London, UK., Russell LJ; Biosciences Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle upon Tyne, UK., Bain R; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle upon Tyne, UK., Moorman AV; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle upon Tyne, UK., Bentley DR; Illumina Cambridge Ltd., Granta Park, Great Abington, Cambridge, UK., Harrison CJ; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle upon Tyne, UK. christine.harrison@newcastle.ac.uk., Ross MT; Illumina Cambridge Ltd., Granta Park, Great Abington, Cambridge, UK. mross@illumina.com.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2023 Mar; Vol. 37 (3), pp. 518-528. Date of Electronic Publication: 2023 Jan 19.
DOI: 10.1038/s41375-022-01806-8
Abstrakt: Childhood B-cell acute lymphoblastic leukaemia (B-ALL) is characterised by recurrent genetic abnormalities that drive risk-directed treatment strategies. Using current techniques, accurate detection of such aberrations can be challenging, due to the rapidly expanding list of key genetic abnormalities. Whole genome sequencing (WGS) has the potential to improve genetic testing, but requires comprehensive validation. We performed WGS on 210 childhood B-ALL samples annotated with clinical and genetic data. We devised a molecular classification system to subtype these patients based on identification of key genetic changes in tumour-normal and tumour-only analyses. This approach detected 294 subtype-defining genetic abnormalities in 96% (202/210) patients. Novel genetic variants, including fusions involving genes in the MAP kinase pathway, were identified. WGS results were concordant with standard-of-care methods and whole transcriptome sequencing (WTS). We expanded the catalogue of genetic profiles that reliably classify PAX5alt and ETV6::RUNX1-like subtypes. Our novel bioinformatic pipeline improved detection of DUX4 rearrangements (DUX4-r): a good-risk B-ALL subtype with high survival rates. Overall, we have validated that WGS provides a standalone, reliable genetic test to detect all subtype-defining genetic abnormalities in B-ALL, accurately classifying patients for the risk-directed treatment stratification, while simultaneously performing as a research tool to identify novel disease biomarkers.
(© 2023. The Author(s).)
Databáze: MEDLINE
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