RNA-sequencing data from 195 B-cell precursor acute lymphoblastic leukemias and mate pair whole genome sequencing data from 15 B-cell precursor acute lymphoblastic leukemias

Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). Using RNA-sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a new 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. Taken together, this study provides a detailed overview of fusion genes in pediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide novel therapeutic options in this disease.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 12 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001002112	RNA-seq data from 195 pediatric BCP-ALL cases. Alignment: TopHat 2.0.7. Reference genome: hg19.	Illumina HiScanSQ	195
EGAD00001002113	Mate pair whole genome sequencing data from 15 pediatric BCP ALL cases. Reference genome: hg19. Alignment: BWA 0.7.9a.	NextSeq 500	15

Publications	Citations
Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia. 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: 2016 11790	220
Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia. Gunnarsson R, Dilorenzo S, Lundin-Ström KB, Olsson L, Biloglav A, Lilljebjörn H, Rissler M, Wahlberg P, Lundmark A, Castor A, Behrendtz M, Fioretos T, Paulsson K, Isaksson A, Johansson B. Leukemia 32: 2018 2117-2125	4
Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia. Yang M, Vesterlund M, Siavelis I, Moura-Castro LH, Castor A, Fioretos T, Jafari R, Lilljebjörn H, Odom DT, Olsson L, Ravi N, Woodward EL, Harewood L, Lehtiö J, Paulsson K. Nat Commun 10: 2019 1519	59
DUX4 Suppresses MHC Class I to Promote Cancer Immune Evasion and Resistance to Checkpoint Blockade. Chew GL, Campbell AE, De Neef E, Sutliff NA, Shadle SC, Tapscott SJ, Bradley RK. Dev Cell 50: 2019 658-671.e7	77
The application of RNA sequencing for the diagnosis and genomic classification of pediatric acute lymphoblastic leukemia. Brown LM, Lonsdale A, Zhu A, Davidson NM, Schmidt B, Hawkins A, Wallach E, Martin M, Mechinaud FM, Khaw SL, Bartolo RC, Ludlow LEA, Challis J, Brooks I, Petrovic V, Venn NC, Sutton R, Majewski IJ, Oshlack A, Ekert PG. Blood Adv 4: 2020 930-942	54
Sister chromatid cohesion defects are associated with chromosomal copy number heterogeneity in high hyperdiploid childhood acute lymphoblastic leukemia. Moura-Castro LH, Peña-Martínez P, Castor A, Galeev R, Larsson J, Järås M, Yang M, Paulsson K. Genes Chromosomes Cancer 60: 2021 410-417	9
Short H2A histone variants are expressed in cancer. Chew GL, Bleakley M, Bradley RK, Malik HS, Henikoff S, Molaro A, Sarthy J. Nat Commun 12: 2021 490	32
ALLSorts: an RNA-Seq subtype classifier for B-cell acute lymphoblastic leukemia. Schmidt B, Brown LM, Ryland GL, Lonsdale A, Kosasih HJ, Ludlow LE, Majewski IJ, Blombery P, Ekert PG, Davidson NM, Oshlack A. Blood Adv 6: 2022 4093-4097	37
A convergent malignant phenotype in B-cell acute lymphoblastic leukemia involving the splicing factor SRRM1. Closa A, Reixachs-Solé M, Fuentes-Fayos AC, Hayer KE, Melero JL, Adriaanse FRS, Bos RS, Torres-Diz M, Hunger SP, Roberts KG, Mullighan CG, Stam RW, Thomas-Tikhonenko A, Castaño JP, Luque RM, Eyras E. NAR Cancer 4: 2022 zcac041	9
DUX4 is a common driver of immune evasion and immunotherapy failure in metastatic cancers. Pineda JMB, Bradley RK. Elife 12: 2024 RP89017	5
Integrative alternative splicing analysis reveals new prognosis signature in B-cell acute lymphoblastic leukemia. Zhuo Z, Wang J, Zhang Y, Meng G. Int J Biol Sci 20: 2024 4496-4512	1
Characterizing the allele-specific gene expression landscape in high hyperdiploid acute lymphoblastic leukemia with BASE. Andersson J, Aydın E, Gunnarsson R, Lilljebjörn H, Fioretos T, Johansson B, Paulsson K, Yang M. Sci Rep 14: 2024 23181	0