Genomic_profiling_of_B_other_Adult_ALL_WGS

Adult ALL is an aggressive leukaemia, affecting adults of all ages. It is associated with a rapid onset and poor outcomes. Our understanding of adult ALL genome has been limited to molecular markers first described in paediatric ALL and validated in adult ALL and to date there have been no studies investigating the genomics of Adult ALL. We will perform whole genome sequencing on at least 100 Adult ALL cases. Priority will be given on ALL cases without a known primary lesion by cytogenetic analysis which are categorised as “B-other”. We will also sequence representative cases of each known subtype. This will deliver a comprehensive annotation of the genomic landscape of Adult ALL to include acquired somatic mutations (substitutions, indels, structural variants/fusion genes) and copy number profiles. The focus on B-other Adult ALL is likely to result in new and previously undescribed genomic lesions.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001009304	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, underlied by 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.	HiSeq X Ten	115

Publications	Citations
Diagnostic utility of whole genome sequencing in adults with B-other acute lymphoblastic leukemia. Leongamornlert D, Gutiérrez-Abril J, Lee S, Barretta E, Creasey T, Gundem G, Levine MF, Arango-Ossa JE, Liosis K, Medina-Martinez JS, Zuborne Alapi K, Kirkwood AA, Clifton-Hadley L, Patrick P, Jones D, O'Neill L, Butler AP, Harrison CJ, Campbell P, Patel B, Moorman AV, Fielding AK, Papaemmanuil E. Blood Adv 7: 2023 3862-3873	5

Publications

Citations

Diagnostic utility of whole genome sequencing in adults with B-other acute lymphoblastic leukemia.
Leongamornlert D, Gutiérrez-Abril J, Lee S, Barretta E, Creasey T, Gundem G, Levine MF, Arango-Ossa JE, Liosis K, Medina-Martinez JS, Zuborne Alapi K, Kirkwood AA, Clifton-Hadley L, Patrick P, Jones D, O'Neill L, Butler AP, Harrison CJ, Campbell P, Patel B, Moorman AV, Fielding AK, Papaemmanuil E. Blood Adv 7: 2023 3862-3873