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Lookup NU author(s): Dr Tom Creasey, Dr Amir EnshaeiORCiD, Claire Schwab, Kathryn Watts, Gavin Cuthbert, Professor Anthony MoormanORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Low hypodiploidy (30‐39 chromosomes) is one of the most prevalent genetic subtypes among adults with ALL and is associated with a very poor outcome. Low hypodiploid clones can often undergo a chromosomal doubling generating a near‐triploid clone (60‐78 chromosomes). When cytogenetic techniques detect a near triploid clone, a diagnostic challenge may ensue in differentiating presumed duplicated low hypodiploidy from good risk high hyperdiploid ALL (51‐67 chromosomes). We used single‐nucleotide polymorphism (SNP) arrays to analyze low hypodiploid/near triploid (HoTr) (n=48) and high hyperdiploid (HeH) (n=40) cases. In addition to standard analysis, we derived log2 ratios for entire chromosomes enabling us to analyze the cohort using machine‐learning techniques. Low hypodiploid and near triploid cases clustered together and separately from high hyperdiploid samples. Using these approaches, we also identified three cases with 50‐60 chromosomes, originally called as HeH, which were, in fact, HoTr and two cases incorrectly called as HoTr. TP53 mutation analysis supported the new classification of all cases tested. Next, we constructed a classification and regression tree model for predicting ploidy status with chromosomes 1, 7 and 14 being the key discriminators. The classifier correctly identified 47/50 (94%) HoTr cases. We validated the classifier using an independent cohort of 44 cases where it correctly called 7/7 (100%) low hypodiploid cases. The results of this study suggest that HoTr is more frequent among older adults with ALL than previously estimated and that SNP array analysis should accompany cytogenetics where possible. The classifier can assist where SNP array patterns are challenging to interpret.
Author(s): Creasey T, Enshaei A, Nebral K, Schwab C, Watts K, Cuthbert G, Vora A, Moppett J, Harrison CJ, Fielding AD, Haas OA, Moorman AV
Publication type: Article
Publication status: Published
Journal: Genes Chromosomes Cancer
Year: 2021
Volume: 60
Issue: 9
Pages: 604-615
Print publication date: 01/09/2021
Online publication date: 03/05/2021
Acceptance date: 26/04/2021
Date deposited: 03/08/2022
ISSN (print): 1045-2257
ISSN (electronic): 1098-2264
Publisher: Wiley
URL: https://doi.org/10.1002/gcc.22956
DOI: 10.1002/gcc.22956
PubMed id: 33938069
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