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Single nucleotide polymorphism array‐based signature of low hypodiploidy in acute lymphoblastic leukemia
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 detec...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600946/ https://www.ncbi.nlm.nih.gov/pubmed/33938069 http://dx.doi.org/10.1002/gcc.22956 |
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author | Creasey, Thomas Enshaei, Amir Nebral, Karin Schwab, Claire Watts, Kathryn Cuthbert, Gavin Vora, Ajay Moppett, John Harrison, Christine J. Fielding, Adele K. Haas, Oskar A. Moorman, Anthony V. |
author_facet | Creasey, Thomas Enshaei, Amir Nebral, Karin Schwab, Claire Watts, Kathryn Cuthbert, Gavin Vora, Ajay Moppett, John Harrison, Christine J. Fielding, Adele K. Haas, Oskar A. Moorman, Anthony V. |
author_sort | Creasey, Thomas |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8600946 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86009462021-11-23 Single nucleotide polymorphism array‐based signature of low hypodiploidy in acute lymphoblastic leukemia Creasey, Thomas Enshaei, Amir Nebral, Karin Schwab, Claire Watts, Kathryn Cuthbert, Gavin Vora, Ajay Moppett, John Harrison, Christine J. Fielding, Adele K. Haas, Oskar A. Moorman, Anthony V. Genes Chromosomes Cancer Research Articles 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. John Wiley & Sons, Inc. 2021-05-17 2021-09 /pmc/articles/PMC8600946/ /pubmed/33938069 http://dx.doi.org/10.1002/gcc.22956 Text en © 2021 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Creasey, Thomas Enshaei, Amir Nebral, Karin Schwab, Claire Watts, Kathryn Cuthbert, Gavin Vora, Ajay Moppett, John Harrison, Christine J. Fielding, Adele K. Haas, Oskar A. Moorman, Anthony V. Single nucleotide polymorphism array‐based signature of low hypodiploidy in acute lymphoblastic leukemia |
title | Single nucleotide polymorphism array‐based signature of low hypodiploidy in acute lymphoblastic leukemia |
title_full | Single nucleotide polymorphism array‐based signature of low hypodiploidy in acute lymphoblastic leukemia |
title_fullStr | Single nucleotide polymorphism array‐based signature of low hypodiploidy in acute lymphoblastic leukemia |
title_full_unstemmed | Single nucleotide polymorphism array‐based signature of low hypodiploidy in acute lymphoblastic leukemia |
title_short | Single nucleotide polymorphism array‐based signature of low hypodiploidy in acute lymphoblastic leukemia |
title_sort | single nucleotide polymorphism array‐based signature of low hypodiploidy in acute lymphoblastic leukemia |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600946/ https://www.ncbi.nlm.nih.gov/pubmed/33938069 http://dx.doi.org/10.1002/gcc.22956 |
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