Transcriptional and Mutational Profiling of B-Other Acute Lymphoblastic Leukemia for Improved Diagnostics

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common cancer in children, and significant progress has been made in diagnostics and the treatment of this disease based on the subtypes of BCP-ALL. However, in a large proportion of cases (B-other), recurrent BCP-ALL-associated gen...

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Autores principales:	Philippe Chouvarine, Željko Antić, Jana Lentes, Charlotte Schröder, Julia Alten, Monika Brüggemann, Enrique Carrillo-de Santa Pau, Thomas Illig, Teresa Laguna, Denis Schewe, Martin Stanulla, Ming Tang, Martin Zimmermann, Martin Schrappe, Brigitte Schlegelberger, Gunnar Cario, Anke K. Bergmann
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	whole-transcriptome sequencing B-cell precursor acute lymphoblastic leukemia gene fusions treatment stratification biomarkers Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5844b8801bad46869a44b4eedbef90a3
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spelling	oai:doaj.org-article:5844b8801bad46869a44b4eedbef90a32021-11-25T17:02:15ZTranscriptional and Mutational Profiling of B-Other Acute Lymphoblastic Leukemia for Improved Diagnostics10.3390/cancers132256532072-6694https://doaj.org/article/5844b8801bad46869a44b4eedbef90a32021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5653https://doaj.org/toc/2072-6694B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common cancer in children, and significant progress has been made in diagnostics and the treatment of this disease based on the subtypes of BCP-ALL. However, in a large proportion of cases (B-other), recurrent BCP-ALL-associated genomic alterations remain unidentifiable by current diagnostic procedures. In this study, we performed RNA sequencing and analyzed gene fusions, expression profiles, and mutations in diagnostic samples of 185 children with BCP-ALL. Gene expression clustering showed that a subset of B-other samples partially clusters with some of the known subgroups, particularly <i>DUX4</i>-positive. Mutation analysis coupled with gene expression profiling revealed the presence of distinctive BCP-ALL subgroups, characterized by the presence of mutations in known ALL driver genes, e.g., <i>PAX5</i> and <i>IKZF1</i>. Moreover, we identified novel fusion partners of lymphoid lineage transcriptional factors <i>ETV6</i>, <i>IKZF1</i> and <i>PAX5</i>. In addition, we report on low blast count detection thresholds and show that the use of EDTA tubes for sample collection does not have adverse effects on sequencing and downstream analysis. Taken together, our findings demonstrate the applicability of whole-transcriptome sequencing for personalized diagnostics in pediatric ALL, including tentative classification of the B-other cases that are difficult to diagnose using conventional methods.Philippe ChouvarineŽeljko AntićJana LentesCharlotte SchröderJulia AltenMonika BrüggemannEnrique Carrillo-de Santa PauThomas IlligTeresa LagunaDenis ScheweMartin StanullaMing TangMartin ZimmermannMartin SchrappeBrigitte SchlegelbergerGunnar CarioAnke K. BergmannMDPI AGarticlewhole-transcriptome sequencingB-cell precursor acute lymphoblastic leukemiagene fusionstreatment stratification biomarkersNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5653, p 5653 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	whole-transcriptome sequencing B-cell precursor acute lymphoblastic leukemia gene fusions treatment stratification biomarkers Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	whole-transcriptome sequencing B-cell precursor acute lymphoblastic leukemia gene fusions treatment stratification biomarkers Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Philippe Chouvarine Željko Antić Jana Lentes Charlotte Schröder Julia Alten Monika Brüggemann Enrique Carrillo-de Santa Pau Thomas Illig Teresa Laguna Denis Schewe Martin Stanulla Ming Tang Martin Zimmermann Martin Schrappe Brigitte Schlegelberger Gunnar Cario Anke K. Bergmann Transcriptional and Mutational Profiling of B-Other Acute Lymphoblastic Leukemia for Improved Diagnostics
description	B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common cancer in children, and significant progress has been made in diagnostics and the treatment of this disease based on the subtypes of BCP-ALL. However, in a large proportion of cases (B-other), recurrent BCP-ALL-associated genomic alterations remain unidentifiable by current diagnostic procedures. In this study, we performed RNA sequencing and analyzed gene fusions, expression profiles, and mutations in diagnostic samples of 185 children with BCP-ALL. Gene expression clustering showed that a subset of B-other samples partially clusters with some of the known subgroups, particularly <i>DUX4</i>-positive. Mutation analysis coupled with gene expression profiling revealed the presence of distinctive BCP-ALL subgroups, characterized by the presence of mutations in known ALL driver genes, e.g., <i>PAX5</i> and <i>IKZF1</i>. Moreover, we identified novel fusion partners of lymphoid lineage transcriptional factors <i>ETV6</i>, <i>IKZF1</i> and <i>PAX5</i>. In addition, we report on low blast count detection thresholds and show that the use of EDTA tubes for sample collection does not have adverse effects on sequencing and downstream analysis. Taken together, our findings demonstrate the applicability of whole-transcriptome sequencing for personalized diagnostics in pediatric ALL, including tentative classification of the B-other cases that are difficult to diagnose using conventional methods.
format	article
author	Philippe Chouvarine Željko Antić Jana Lentes Charlotte Schröder Julia Alten Monika Brüggemann Enrique Carrillo-de Santa Pau Thomas Illig Teresa Laguna Denis Schewe Martin Stanulla Ming Tang Martin Zimmermann Martin Schrappe Brigitte Schlegelberger Gunnar Cario Anke K. Bergmann
author_facet	Philippe Chouvarine Željko Antić Jana Lentes Charlotte Schröder Julia Alten Monika Brüggemann Enrique Carrillo-de Santa Pau Thomas Illig Teresa Laguna Denis Schewe Martin Stanulla Ming Tang Martin Zimmermann Martin Schrappe Brigitte Schlegelberger Gunnar Cario Anke K. Bergmann
author_sort	Philippe Chouvarine
title	Transcriptional and Mutational Profiling of B-Other Acute Lymphoblastic Leukemia for Improved Diagnostics
title_short	Transcriptional and Mutational Profiling of B-Other Acute Lymphoblastic Leukemia for Improved Diagnostics
title_full	Transcriptional and Mutational Profiling of B-Other Acute Lymphoblastic Leukemia for Improved Diagnostics
title_fullStr	Transcriptional and Mutational Profiling of B-Other Acute Lymphoblastic Leukemia for Improved Diagnostics
title_full_unstemmed	Transcriptional and Mutational Profiling of B-Other Acute Lymphoblastic Leukemia for Improved Diagnostics
title_sort	transcriptional and mutational profiling of b-other acute lymphoblastic leukemia for improved diagnostics
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5844b8801bad46869a44b4eedbef90a3
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Transcriptional and Mutational Profiling of B-Other Acute Lymphoblastic Leukemia for Improved Diagnostics

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