Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia

Henrik Lilljebjörn; Rasmus Henningsson; Axel Hyrenius-Wittsten; Linda Olsson; Christina Orsmark-Pietras; Sofia Von Palffy; Maria Askmyr; Marianne Rissler; Martin Schrappe; Gunnar Cario; Anders Castor; Kees-Jan Pronk; Mikael Behrendtz; Felix Mitelman; Bertil Johansson; Kajsa Paulsson; Anna K. Andersson; Magnus Fontes; Thoas Fioretos

doi:10.1038/ncomms11790

Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia

Henrik Lilljebjörn, Rasmus Henningsson, Axel Hyrenius-Wittsten, Linda Olsson, Christina Orsmark-Pietras, Sofia Von Palffy, Maria Askmyr, Marianne Rissler, Martin Schrappe, Gunnar Cario, Anders Castor, Kees-Jan Pronk, Mikael Behrendtz, Felix Mitelman, Bertil Johansson, Kajsa Paulsson, Anna K. Andersson, Magnus Fontes, Thoas Fioretos

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	11790
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11790
Publication status	Published - 2016 Jun 6

Subject classification (UKÄ)

Medical Genetics

Access to Document

10.1038/ncomms11790

Cite this

Lilljebjörn, H., Henningsson, R., Hyrenius-Wittsten, A., Olsson, L., Orsmark-Pietras, C., Von Palffy, S., Askmyr, M., Rissler, M., Schrappe, M., Cario, G., Castor, A., Pronk, K-J., Behrendtz, M., Mitelman, F., Johansson, B., Paulsson, K., Andersson, A. K., Fontes, M., & Fioretos, T. (2016). Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia. Nature Communications, 7, [11790]. https://doi.org/10.1038/ncomms11790

@article{cdebe51384d8452183178265a856617a,

title = "Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia",

abstract = "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.",

author = "Henrik Lilljebj{\"o}rn and Rasmus Henningsson and Axel Hyrenius-Wittsten and Linda Olsson and Christina Orsmark-Pietras and {Von Palffy}, Sofia and Maria Askmyr and Marianne Rissler and Martin Schrappe and Gunnar Cario and Anders Castor and Kees-Jan Pronk and Mikael Behrendtz and Felix Mitelman and Bertil Johansson and Kajsa Paulsson and Andersson, {Anna K.} and Magnus Fontes and Thoas Fioretos",

year = "2016",

month = jun,

day = "6",

doi = "10.1038/ncomms11790",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Lilljebjörn, H , Henningsson, R , Hyrenius-Wittsten, A , Olsson, L , Orsmark-Pietras, C , Von Palffy, S, Askmyr, M, Rissler, M, Schrappe, M, Cario, G, Castor, A , Pronk, K-J, Behrendtz, M, Mitelman, F , Johansson, B , Paulsson, K , Andersson, AK , Fontes, M & Fioretos, T 2016, 'Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia', Nature Communications, vol. 7, 11790. https://doi.org/10.1038/ncomms11790

TY - JOUR

T1 - Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia

AU - Lilljebjörn, Henrik

AU - Henningsson, Rasmus

AU - Hyrenius-Wittsten, Axel

AU - Olsson, Linda

AU - Orsmark-Pietras, Christina

AU - Von Palffy, Sofia

AU - Askmyr, Maria

AU - Rissler, Marianne

AU - Schrappe, Martin

AU - Cario, Gunnar

AU - Castor, Anders

AU - Pronk, Kees-Jan

AU - Behrendtz, Mikael

AU - Mitelman, Felix

AU - Johansson, Bertil

AU - Paulsson, Kajsa

AU - Andersson, Anna K.

AU - Fontes, Magnus

AU - Fioretos, Thoas

PY - 2016/6/6

Y1 - 2016/6/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84973305001&partnerID=8YFLogxK

U2 - 10.1038/ncomms11790

DO - 10.1038/ncomms11790

M3 - Article

C2 - 27265895

AN - SCOPUS:84973305001

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 11790

ER -

Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia

Abstract

Subject classification (UKÄ)

Access to Document

Other files and links

Fingerprint

Dimension Reduction and Signal Decomposition for Genotype–Phenotype Relations

Molecular Interrogation and Functional Studies of Acute Leukemia

Cite this