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

Summary, in English

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 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
• Department/s: The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy; Aneuploidy in cancer; Translational Genomic and Functional Studies of Leukemia; Division of Clinical Genetics; Mathematics (Faculty of Engineering); Paediatrics (Lund); Hematopoietic and immunologic developement; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation; Division of Molecular Hematology (DMH)
• Publishing year: 2016-06-06
• Language: English
• Publication/Series: Nature Communications
• Volume: 7
• Links: http://dx.doi.org/10.1038/ncomms11790
• Document type: Journal article
• Publisher: Nature Publishing Group
• Topic: Medical Genetics
• Status: Published
• Research group: The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy; Aneuploidy in cancer; Translational Genomic and Functional Studies of Leukemia; Hematopoietic and immunologic developement
• ISBN/ISSN/Other: ISSN: 2041-1723