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

Lilljebjörn, Henrik LU ; Henningsson, Rasmus LU ; Hyrenius-Wittsten, Axel LU ; Olsson, Linda LU ; Orsmark-Pietras, Christina LU ; Von Palffy, Sofia LU ; Askmyr, Maria LU ; Rissler, Marianne LU ; Schrappe, Martin and Cario, Gunnar, et al. (2016) In Nature Communications 7.
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... (More)

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.

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Please use this url to cite or link to this publication:
@article{cdebe513-84d8-4521-8317-8265a856617a,
  abstract     = {<p>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.</p>},
  articleno    = {11790},
  author       = {Lilljebjörn, Henrik and Henningsson, Rasmus and Hyrenius-Wittsten, Axel and Olsson, Linda and Orsmark-Pietras, Christina and Von Palffy, Sofia and Askmyr, Maria and Rissler, Marianne and Schrappe, Martin and Cario, Gunnar and Castor, Anders and Pronk, Kees-Jan and Behrendtz, Mikael and Mitelman, Felix and Johansson, Bertil and Paulsson, Kajsa and Andersson, Anna K. and Fontes, Magnus and Fioretos, Thoas},
  issn         = {2041-1723},
  language     = {eng},
  month        = {06},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia},
  url          = {http://dx.doi.org/10.1038/ncomms11790},
  volume       = {7},
  year         = {2016},
}