In:
Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-8-14)
Abstract:
The suitability of whole-genome sequencing (WGS) as the sole method to detect clinically relevant genomic aberrations in B-cell acute lymphoblastic leukemia (ALL) was investigated with the aim of replacing current diagnostic methods. Methods For this purpose, we assessed the analytical performance of 150 bp paired-end WGS (90x leukemia/30x germline). A set of 88 retrospective B-cell ALL samples were selected to represent established ALL subgroups as well as ALL lacking stratifying markers by standard-of-care (SoC), so-called B-other ALL. Results Both the analysis of paired leukemia/germline (L/N)(n=64) as well as leukemia-only (L-only)(n=88) detected all types of aberrations mandatory in the current ALLTogether trial protocol, i.e., aneuploidies, structural variants, and focal copy-number aberrations. Moreover, comparison to SoC revealed 100% concordance and that all patients had been assigned to the correct genetic subgroup using both approaches. Notably, WGS could allocate 35 out of 39 B-other ALL samples to one of the emerging genetic subgroups considered in the most recent classifications of ALL. We further investigated the impact of high (90x; n=58) vs low (30x; n=30) coverage on the diagnostic yield and observed an equally perfect concordance with SoC; low coverage detected all relevant lesions. Discussion The filtration of the WGS findings with a short list of genes recurrently rearranged in ALL was instrumental to extract the clinically relevant information efficiently. Nonetheless, the detection of DUX4 rearrangements required an additional customized analysis, due to multiple copies of this gene embedded in the highly repetitive D4Z4 region. We conclude that the diagnostic performance of WGS as the standalone method was remarkable and allowed detection of all clinically relevant genomic events in the diagnostic setting of B-cell ALL.
Type of Medium:
Online Resource
ISSN:
2234-943X
DOI:
10.3389/fonc.2023.1217712
DOI:
10.3389/fonc.2023.1217712.s001
DOI:
10.3389/fonc.2023.1217712.s002
DOI:
10.3389/fonc.2023.1217712.s003
DOI:
10.3389/fonc.2023.1217712.s004
DOI:
10.3389/fonc.2023.1217712.s005
DOI:
10.3389/fonc.2023.1217712.s006
DOI:
10.3389/fonc.2023.1217712.s007
DOI:
10.3389/fonc.2023.1217712.s008
DOI:
10.3389/fonc.2023.1217712.s009
DOI:
10.3389/fonc.2023.1217712.s010
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2023
detail.hit.zdb_id:
2649216-7