Whole Genome Sequencing of Neuroblastoma

4 Datasets 1 Publication

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
EGAD00001000196	Neuroblastoma samples	Complete Genomics	203
EGAD00001000202	Neuroblastoma samples (Analyses_vcf files)		204
EGAD00001001360	The majority of neuroblastoma patients have tumors that initially respond to chemotherapy, but a large proportion of patients will experience therapy-resistant relapses. The molecular basis of this aggressive phenotype is unknown. Whole genome sequencing of 23 paired diagnostic and relapsed neuroblastomas showed clonal evolution from the diagnostic tumor with a median of 29 somatic mutations unique to the relapse sample. Eighteen of the 23 relapse tumors (78%) showed RAS-MAPK pathway mutations. Seven events were detected only in the relapse tumor while the others showed clonal enrichment. In neuroblastoma cell lines we also detected a high frequency of activating mutations in the RAS-MAPK pathway (11/18, 61%) and these lesions predicted for sensitivity to MEK inhibition in vitro and in vivo. Our findings provide a rationale for genetic characterization of relapse neuroblastoma and show that RAS-MAPK pathway mutations may function as a biomarker for new therapeutic approaches to refractory disease.		221
EGAD00010000552	Neuroblastoma samples		130

Publications	Citations
Defects in 8-oxo-guanine repair pathway cause high frequency of C > A substitutions in neuroblastoma. van den Boogaard ML, Oka R, Hakkert A, Schild L, Ebus ME, van Gerven MR, Zwijnenburg DA, Molenaar P, Hoyng LL, Dolman MEM, Essing AHW, Koopmans B, Helleday T, Drost J, van Boxtel R, Versteeg R, Koster J, Molenaar JJ. Proc Natl Acad Sci U S A 118: 2021 e2007898118	11