Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia.
Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL). Using RNA sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. Furthermore, we identify a subtype characterized by an ETV6-RUNX1-like gene-expression profile and coexisting ETV6 and IKZF1 alterations. Thus, this study provides a detailed overview of fusion genes in paediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide therapeutic options for this disease.
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.
Henrik
H
Lilljebjörn
Centre for Mathematical Sciences, Lund University, Lund 22362, Sweden.
Rasmus
R
Henningsson
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.
Axel
A
Hyrenius-Wittsten
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.
Linda
L
Olsson
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.
Christina
C
Orsmark-Pietras
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.
Sofia
S
von Palffy
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.
Maria
M
Askmyr
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.
Marianne
M
Rissler
Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel 24105, Germany.
Martin
M
Schrappe
Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel 24105, Germany.
Gunnar
G
Cario
Department of Pediatrics, Skåne University Hospital, Lund University, Lund 22185, Sweden.
Anders
A
Castor
Department of Pediatrics, Skåne University Hospital, Lund University, Lund 22185, Sweden.
Cornelis J H
CJ
Pronk
Department of Pediatrics, Linköping University Hospital, Linköping 58185, Sweden.
Mikael
M
Behrendtz
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.
Felix
F
Mitelman
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.|Department of Clinical Genetics, University and Regional Laboratories Region Skåne, Lund 22185, Sweden.
Bertil
B
Johansson
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.
Kajsa
0000-0001-7950-222X
K
Paulsson
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.
Anna K
AK
Andersson
Centre for Mathematical Sciences, Lund University, Lund 22362, Sweden.
Magnus
M
Fontes
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.|Department of Clinical Genetics, University and Regional Laboratories Region Skåne, Lund 22185, Sweden.
Thoas
T
Fioretos
D017398:Alternative Splicing / Q000235:genetics; D002648:Child; D019457:Chromosome Breakage; D016000:Cluster Analysis; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement / Q000235:genetics*; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D025341:Principal Component Analysis
C121257:DUX4L1 protein, human; D018398:Homeodomain Proteins; D015514:Oncogene Proteins, Fusion