Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma

Neuroblastomas are tumors of peripheral sympathetic neurons and are the most common solid tumor in children. To determine the genetic basis for neuroblastoma we performed whole-genome sequencing (6 cases), exome sequencing (16 cases), genome-wide rearrangement analyses (32 cases), and targeted analyses of specific genomic loci (40 cases) using massively parallel sequencing. On average each tumor had 19 somatic alterations in coding genes (range, 3-70). Among genes not previously known to be involved in neuroblastoma, chromosomal deletions and sequence alterations of chromatin remodeling genes, ARID1A and ARID1B, were identified in 8 of 71 tumors (11%) and were associated with early treatment failure and decreased survival. Using tumor-specific structural alterations, we developed an approach to identify rearranged DNA fragments in sera, providing personalized biomarkers for minimal residual disease detection and monitoring. These results highlight dysregulation of chromatin remodeling in pediatric tumorigenesis and provide new approaches for the management of neuroblastoma patients.Data Provider: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC)

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

1 Dataset 4 Publications

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Dataset ID	Description	Technology	Samples
EGAD00001000282	Neuroblastomas are tumors of peripheral sympathetic neurons and are the most common solid tumor in children. To determine the genetic basis for neuroblastoma we performed whole-genome sequencing (6 cases), exome sequencing (16 cases), genome-wide rearrangement analyses (32 cases), and targeted analyses of specific genomic loci (40 cases) using massively parallel sequencing. On average each tumor had 19 somatic alterations in coding genes (range, 3-70). Among genes not previously known to be involved in neuroblastoma, chromosomal deletions and sequence alterations of chromatin remodeling genes, ARID1A and ARID1B, were identified in 8 of 71 tumors (11%) and were associated with early treatment failure and decreased survival. Using tumor-specific structural alterations, we developed an approach to identify rearranged DNA fragments in sera, providing personalized biomarkers for minimal residual disease detection and monitoring. These results highlight dysregulation of chromatin remodeling in pediatric tumorigenesis and provide new approaches for the management of neuroblastoma patients.	Illumina Genome Analyzer IIx Illumina HiSeq 2000	114

Publications	Citations
Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma. Sausen M, Leary RJ, Jones S, Wu J, Reynolds CP, Liu X, Blackford A, Parmigiani G, Diaz LA, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE, Hogarty MD. Nat Genet 45: 2013 12-17	276
A comprehensive characterization of rare mitochondrial DNA variants in neuroblastoma. Calabrese FM, Clima R, Pignataro P, Lasorsa VA, Hogarty MD, Castellano A, Conte M, Tonini GP, Iolascon A, Gasparre G, Capasso M. Oncotarget 7: 2016 49246-49258	6
Armadillo repeat containing 12 promotes neuroblastoma progression through interaction with retinoblastoma binding protein 4. Li D, Song H, Mei H, Fang E, Wang X, Yang F, Li H, Chen Y, Huang K, Zheng L, Tong Q. Nat Commun 9: 2018 2829	34
Pancreatic cancer organoids recapitulate disease and allow personalized drug screening. Driehuis E, van Hoeck A, Moore K, Kolders S, Francies HE, Gulersonmez MC, Stigter ECA, Burgering B, Geurts V, Gracanin A, Bounova G, Morsink FH, Vries R, Boj S, van Es J, Offerhaus GJA, Kranenburg O, Garnett MJ, Wessels L, Cuppen E, Brosens LAA, Clevers H. Proc Natl Acad Sci U S A 116: 2019 26580-26590	215