دورية أكاديمية
Diagnostic utility of whole genome sequencing in adults with B-other acute lymphoblastic leukemia
| العنوان: | Diagnostic utility of whole genome sequencing in adults with B-other acute lymphoblastic leukemia |
|---|---|
| المؤلفون: | Leongamornlert, Daniel, Gutiérrez-Abril, Jesús, Lee, Soo Wah, Barretta, Emilio, Creasey, Tom, Gundem, Gunes, Levine, Max Fine, Arango Ossa, Juan Esteban, Liosis, Konstantinos, Medina-Martinez, Juan Santiago, Zuborne Alapi, Krisztina, Kirkwood, Amy A, Clifton-Hadley, Laura, Patrick, Pip, Jones, David, O'Neill, Laura J, Butler, Adam P, Harrison, Christine J, Campbell, Peter J, Patel, Bela, Moorman, Anthony V, Fielding, Adele K, Papaemmanuil, Elli |
| المصدر: | Blood Advances (2023) (In press). |
| بيانات النشر: | American Society of Hematology |
| سنة النشر: | 2023 |
| المجموعة: | University College London: UCL Discovery |
| الوصف: | Genomic profiling at diagnosis of B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL) in adults is used to guide disease classification, risk stratification and treatment decisions. Patients for which diagnostic screening fails to identify disease defining or risk stratifying lesions are classified as B-other ALL. We screened a cohort of 652 BCP-ALL cases enrolled in UKALL14 to identify and perform whole genome sequencing (WGS) on paired tumor-normal samples. For 52 B-other patients we compared WGS findings to data from clinical and research cytogenetics. WGS identifies a cancer associated event in 51/52 cases, this includes an established subtype defining genetic alteration in 5/52 that were previously missed by standard-of-care genetics. Of the 47 true B-other ALL we identified a recurrent driver in 87% (41). Complex karyotype by cytogenetics emerges as a heterogeneous group, including distinct genetic alterations associated with either favorable (DUX4-r) or poor outcomes (MEF2D-r, IGK::BCL2). For a subset of 31 cases, we integrate findings from RNA-sequencing (RNA-seq) analysis to include fusion gene detection, and classification by gene expression. Compared to RNA-seq, WGS was sufficient to detect and resolve recurrent genetic subtypes, however RNA-seq can provide orthogonal validation of findings. In conclusion, we demonstrate that WGS can identify clinically relevant genetic abnormalities missed by standard-of-care testing and identify leukemia driver events in virtually all cases of B-other ALL. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/10166175/2/Fielding_bloodadvances.2022008992.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10166175Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/10166175/2/Fielding_bloodadvances.2022008992.pdfTest https://discovery.ucl.ac.uk/id/eprint/10166175Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.143C60D |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |