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 CJ, Behrendtz M, Mitelman F, Johansson B, Paulsson K, Andersson AK, Fontes M, Fioretos T
Nat Commun 7 (-) 11790 [2016-06-06; online 2016-06-06]
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.