Format

Send to

Choose Destination
J Hematol Oncol. 2017 Aug 14;10(1):148. doi: 10.1186/s13045-017-0515-y.

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

Author information

1
Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
2
Department of Pediatrics, Institution for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
3
Clinical Genetics, Uppsala University Hospital, Uppsala, Sweden.
4
Department of Medical Biosciences, University of Umeå, Umeå, Sweden.
5
Karolinska Institutet, Childhood Cancer Research Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
6
Department of Women's and Children's Health, Pediatric Oncology, Uppsala University, Uppsala, Sweden.
7
Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. jessica.nordlund@medsci.uu.se.

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.

KEYWORDS:

BCP-ALL; Fusion genes; Pediatric acute lymphoblastic leukemia; RNA sequencing; T-ALL; Translocation

PMID:
28806978
PMCID:
PMC5557398
DOI:
10.1186/s13045-017-0515-y
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center