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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2017

Open Access 01-12-2017 | Research

Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles

Authors: Yanara Marincevic-Zuniga, Johan Dahlberg, Sara Nilsson, Amanda Raine, Sara Nystedt, Carl Mårten Lindqvist, Eva C. Berglund, Jonas Abrahamsson, Lucia Cavelier, Erik Forestier, Mats Heyman, Gudmar Lönnerholm, Jessica Nordlund, Ann-Christine Syvänen

Published in: Journal of Hematology & Oncology | Issue 1/2017

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Abstract

Background

Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts.

Methods

We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes.

Results

We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations.

Conclusion

Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.
Appendix
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Metadata
Title
Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles
Authors
Yanara Marincevic-Zuniga
Johan Dahlberg
Sara Nilsson
Amanda Raine
Sara Nystedt
Carl Mårten Lindqvist
Eva C. Berglund
Jonas Abrahamsson
Lucia Cavelier
Erik Forestier
Mats Heyman
Gudmar Lönnerholm
Jessica Nordlund
Ann-Christine Syvänen
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2017
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-017-0515-y

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