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Clonal Evolution at First Sight: A Combined Visualization of Diverse Diagnostic Methods Improves Understanding of Leukemic Progression

Patients with myeloid neoplasia are classified by the WHO classification systems. Besides clinical and hematological criteria, cytogenetic and molecular genetic alterations highly impact treatment stratification. In routine diagnostics, a combination of methods is used to decipher different types of...

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Autores principales: Sandmann, Sarah, Behrens, Yvonne Lisa, Davenport, Claudia, Thol, Felicitas, Heuser, Michael, Dörfel, Daniela, Löhr, Friederike, Castrup, Agnes, Steinemann, Doris, Varghese, Julian, Schlegelberger, Brigitte, Dugas, Martin, Göhring, Gudrun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305660/
https://www.ncbi.nlm.nih.gov/pubmed/35875134
http://dx.doi.org/10.3389/fonc.2022.888114
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author Sandmann, Sarah
Behrens, Yvonne Lisa
Davenport, Claudia
Thol, Felicitas
Heuser, Michael
Dörfel, Daniela
Löhr, Friederike
Castrup, Agnes
Steinemann, Doris
Varghese, Julian
Schlegelberger, Brigitte
Dugas, Martin
Göhring, Gudrun
author_facet Sandmann, Sarah
Behrens, Yvonne Lisa
Davenport, Claudia
Thol, Felicitas
Heuser, Michael
Dörfel, Daniela
Löhr, Friederike
Castrup, Agnes
Steinemann, Doris
Varghese, Julian
Schlegelberger, Brigitte
Dugas, Martin
Göhring, Gudrun
author_sort Sandmann, Sarah
collection PubMed
description Patients with myeloid neoplasia are classified by the WHO classification systems. Besides clinical and hematological criteria, cytogenetic and molecular genetic alterations highly impact treatment stratification. In routine diagnostics, a combination of methods is used to decipher different types of genetic variants. Eight patients were comprehensively analyzed using karyotyping, fluorescence in situ hybridization, array-CGH and a custom NGS panel. Clonal evolution was reconstructed manually, integrating all mutational information on single nucleotide variants (SNVs), insertions and deletions (indels), structural variants and copy number variants (CNVs). To allow a correct integration, we differentiate between three scenarios: 1) CNV occurring prior to the SNV/indel, but in the same cells. 2) SNV/indel occurring prior to the CNV, but in the same cells. 3) SNV/indel and CNV existing in parallel, independent of each other. Applying this bioinformatics approach, we reconstructed clonal evolution for all patients. This generalizable approach offers the possibility to integrate various data to analyze identification of driver and passenger mutations as well as possible targets for personalized medicine approaches. Furthermore, this model can be used to identify markers to assess the minimal residual disease.
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spelling pubmed-93056602022-07-23 Clonal Evolution at First Sight: A Combined Visualization of Diverse Diagnostic Methods Improves Understanding of Leukemic Progression Sandmann, Sarah Behrens, Yvonne Lisa Davenport, Claudia Thol, Felicitas Heuser, Michael Dörfel, Daniela Löhr, Friederike Castrup, Agnes Steinemann, Doris Varghese, Julian Schlegelberger, Brigitte Dugas, Martin Göhring, Gudrun Front Oncol Oncology Patients with myeloid neoplasia are classified by the WHO classification systems. Besides clinical and hematological criteria, cytogenetic and molecular genetic alterations highly impact treatment stratification. In routine diagnostics, a combination of methods is used to decipher different types of genetic variants. Eight patients were comprehensively analyzed using karyotyping, fluorescence in situ hybridization, array-CGH and a custom NGS panel. Clonal evolution was reconstructed manually, integrating all mutational information on single nucleotide variants (SNVs), insertions and deletions (indels), structural variants and copy number variants (CNVs). To allow a correct integration, we differentiate between three scenarios: 1) CNV occurring prior to the SNV/indel, but in the same cells. 2) SNV/indel occurring prior to the CNV, but in the same cells. 3) SNV/indel and CNV existing in parallel, independent of each other. Applying this bioinformatics approach, we reconstructed clonal evolution for all patients. This generalizable approach offers the possibility to integrate various data to analyze identification of driver and passenger mutations as well as possible targets for personalized medicine approaches. Furthermore, this model can be used to identify markers to assess the minimal residual disease. Frontiers Media S.A. 2022-07-08 /pmc/articles/PMC9305660/ /pubmed/35875134 http://dx.doi.org/10.3389/fonc.2022.888114 Text en Copyright © 2022 Sandmann, Behrens, Davenport, Thol, Heuser, Dörfel, Löhr, Castrup, Steinemann, Varghese, Schlegelberger, Dugas and Göhring https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Sandmann, Sarah
Behrens, Yvonne Lisa
Davenport, Claudia
Thol, Felicitas
Heuser, Michael
Dörfel, Daniela
Löhr, Friederike
Castrup, Agnes
Steinemann, Doris
Varghese, Julian
Schlegelberger, Brigitte
Dugas, Martin
Göhring, Gudrun
Clonal Evolution at First Sight: A Combined Visualization of Diverse Diagnostic Methods Improves Understanding of Leukemic Progression
title Clonal Evolution at First Sight: A Combined Visualization of Diverse Diagnostic Methods Improves Understanding of Leukemic Progression
title_full Clonal Evolution at First Sight: A Combined Visualization of Diverse Diagnostic Methods Improves Understanding of Leukemic Progression
title_fullStr Clonal Evolution at First Sight: A Combined Visualization of Diverse Diagnostic Methods Improves Understanding of Leukemic Progression
title_full_unstemmed Clonal Evolution at First Sight: A Combined Visualization of Diverse Diagnostic Methods Improves Understanding of Leukemic Progression
title_short Clonal Evolution at First Sight: A Combined Visualization of Diverse Diagnostic Methods Improves Understanding of Leukemic Progression
title_sort clonal evolution at first sight: a combined visualization of diverse diagnostic methods improves understanding of leukemic progression
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305660/
https://www.ncbi.nlm.nih.gov/pubmed/35875134
http://dx.doi.org/10.3389/fonc.2022.888114
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