Deregulation of DUX4 and ERG in acute lymphoblastic leukemia

Chromosomal rearrangements deregulating hematopoietic transcription factors are common leukemia-initiating lesions in acute lymphoblastic leukemia (ALL). Here, we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG are hallmarks of a subtype of B-progenitor ALL with a distinct gene expression profile that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression is present in all cases, and is accompanied by profound transcriptional deregulation of ERG, frequent ERG deletion and expression of a truncated ERG isoform, ERGalt. ERGalt utilizes a non-canonical first exon that is bound by DUX4 and induces its expression....

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

3 Datasets 11 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
EGAD00001002654	This dataset contains RNA-seq, ATAC-seq, and ChIP-seq samples from the SJERG cohort. We applied ChIP-Seq for Dux4 on two B-cell ALL cell-lines(REH, Nalm6) along with INPUT. ATAC-Seq on two B-cell ALL cell-lines(REH, Nalm6) and xenograft of a B-cell ALL patient(ERG000016).	Illumina HiSeq 2000	13
EGAD00001002681	RNA-seq, ChIP-seq, and ATAC-seq files for PCGP SJERG paper titled "Deregulation of DUX4 and ERG in acute lymphoblastic leukemia"	Illumina HiSeq 2000	53
EGAD00001002741	Additional Xenograph files for PCGP SJERG	Illumina HiSeq 2000	11

Publications	Citations
PAX5-driven subtypes of B-progenitor acute lymphoblastic leukemia. Gu Z, Churchman ML, Roberts KG, Moore I, Zhou X, Nakitandwe J, Hagiwara K, Pelletier S, Gingras S, Berns H, Payne-Turner D, Hill A, Iacobucci I, Shi L, Pounds S, Cheng C, Pei D, Qu C, Newman S, Devidas M, Dai Y, Reshmi SC, Gastier-Foster J, Raetz EA, Borowitz MJ, Wood BL, Carroll WL, Zweidler-McKay PA, Rabin KR, Mattano LA, Maloney KW, Rambaldi A, Spinelli O, Radich JP, Minden MD, Rowe JM, Luger S, Litzow MR, Tallman MS, Racevskis J, Zhang Y, Bhatia R, Kohlschmidt J, Mrózek K, Bloomfield CD, Stock W, Kornblau S, Kantarjian HM, Konopleva M, Evans WE, Jeha S, Pui CH, Yang J, Paietta E, Downing JR, Relling MV, Zhang J, Loh ML, Hunger SP, Mullighan CG. Nat Genet 51: 2019 296-307	361
Pediatric patients with acute lymphoblastic leukemia generate abundant and functional neoantigen-specific CD8+ T cell responses. Zamora AE, Crawford JC, Allen EK, Guo XJ, Bakke J, Carter RA, Abdelsamed HA, Moustaki A, Li Y, Chang TC, Awad W, Dallas MH, Mullighan CG, Downing JR, Geiger TL, Chen T, Green DR, Youngblood BA, Zhang J, Thomas PG. Sci Transl Med 11: 2019 eaat8549	53
Long-read sequencing unveils IGH-DUX4 translocation into the silenced IGH allele in B-cell acute lymphoblastic leukemia. Tian L, Shao Y, Nance S, Dang J, Xu B, Ma X, Li Y, Ju B, Dong L, Newman S, Zhou X, Schreiner P, Tseng E, Hon T, Ashby M, Li C, Easton J, Gruber TA, Zhang J. Nat Commun 10: 2019 2789	18
Functional interrogation of HOXA9 regulome in MLLr leukemia via reporter-based CRISPR/Cas9 screen. Zhang H, Zhang Y, Zhou X, Wright S, Hyle J, Zhao L, An J, Zhao X, Shao Y, Xu B, Lee HM, Chen T, Zhou Y, Chen X, Lu R, Li C. Elife 9: 2020 e57858	28
Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy. Jeha S, Choi J, Roberts KG, Pei D, Coustan-Smith E, Inaba H, Rubnitz JE, Ribeiro RC, Gruber TA, Raimondi SC, Karol SE, Qu C, Brady SW, Gu Z, Yang JJ, Cheng C, Downing JR, Evans WE, Relling MV, Campana D, Mullighan CG, Pui CH. Blood Cancer Discov 2: 2021 326-337	81
DNA crosslinking and recombination-activating genes 1/2 (RAG1/2) are required for oncogenic splicing in acute lymphoblastic leukemia. Zhang H, Cheng N, Li Z, Bai L, Fang C, Li Y, Zhang W, Dong X, Jiang M, Liang Y, Zhang S, Mi J, Zhu J, Zhang Y, Chen SJ, Zhao Y, Weng XQ, Hu W, Chen Z, Huang J, Meng G. Cancer Commun (Lond) 41: 2021 1116-1136	9
Enhancer retargeting of CDX2 and UBTF::ATXN7L3 define a subtype of high-risk B-progenitor acute lymphoblastic leukemia. Kimura S, Montefiori L, Iacobucci I, Zhao Y, Gao Q, Paietta EM, Haferlach C, Laird AD, Mead PE, Gu Z, Stock W, Litzow M, Rowe JM, Luger SM, Hunger SP, Ryland GL, Schmidt B, Ekert PG, Oshlack A, Grimmond SM, Rehn J, Breen J, Yeung D, White DL, Aldoss I, Jabbour EJ, Pui CH, Meggendorfer M, Walter W, Kern W, Haferlach T, Brady S, Zhang J, Roberts KG, Blombery P, Mullighan CG. Blood 139: 2022 3519-3531	33
Acute lymphoblastic leukemia displays a distinct highly methylated genome. Hetzel S, Mattei AL, Kretzmer H, Qu C, Chen X, Fan Y, Wu G, Roberts KG, Luger S, Litzow M, Rowe J, Paietta E, Stock W, Mardis ER, Wilson RK, Downing JR, Mullighan CG, Meissner A. Nat Cancer 3: 2022 768-782	24
The genomic landscape of pediatric acute lymphoblastic leukemia. Brady SW, Roberts KG, Gu Z, Shi L, Pounds S, Pei D, Cheng C, Dai Y, Devidas M, Qu C, Hill AN, Payne-Turner D, Ma X, Iacobucci I, Baviskar P, Wei L, Arunachalam S, Hagiwara K, Liu Y, Flasch DA, Liu Y, Parker M, Chen X, Elsayed AH, Pathak O, Li Y, Fan Y, Michael JR, Rusch M, Wilkinson MR, Foy S, Hedges DJ, Newman S, Zhou X, Wang J, Reilly C, Sioson E, Rice SV, Pastor Loyola V, Wu G, Rampersaud E, Reshmi SC, Gastier-Foster J, Guidry Auvil JM, Gesuwan P, Smith MA, Winick N, Carroll AJ, Heerema NA, Harvey RC, Willman CL, Larsen E, Raetz EA, Borowitz MJ, Wood BL, Carroll WL, Zweidler-McKay PA, Rabin KR, Mattano LA, Maloney KW, Winter SS, Burke MJ, Salzer W, Dunsmore KP, Angiolillo AL, Crews KR, Downing JR, Jeha S, Pui CH, Evans WE, Yang JJ, Relling MV, Gerhard DS, Loh ML, Hunger SP, Zhang J, Mullighan CG. Nat Genet 54: 2022 1376-1389	180
Pharmacotypes across the genomic landscape of pediatric acute lymphoblastic leukemia and impact on treatment response. Lee SHR, Yang W, Gocho Y, John A, Rowland L, Smart B, Williams H, Maxwell D, Hunt J, Yang W, Crews KR, Roberts KG, Jeha S, Cheng C, Karol SE, Relling MV, Rosner GL, Inaba H, Mullighan CG, Pui CH, Evans WE, Yang JJ. Nat Med 29: 2023 170-179	40
Prognostic and Pharmacotypic Heterogeneity of Hyperdiploidy in Childhood ALL. Lee SHR, Ashcraft E, Yang W, Roberts KG, Gocho Y, Rowland L, Inaba H, Karol SE, Jeha S, Crews KR, Mullighan CG, Relling MV, Evans WE, Cheng C, Yang JJ, Pui CH. J Clin Oncol 41: 2023 5422-5432	5