Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors

Study ID Alternative Stable ID Type
EGAS00001000906 Other

Study Description

Blastemal histology in chemotherapy-treated pediatric Wilms tumors (nephroblastoma) is associated with adverse prognosis. In order to find novel therapeutic leads for this subgroup of patients, we analyzed 58 such Wilms tumors by exome and transcriptome analysis and validated our findings in larger independent cohorts. Recurrent mutations identified either somatically or in the germline included a hotspot mutation (Q177R) in the homeodomain of SIX1 and SIX2 in tumors with high proliferative potential, mutations in microprocessor genes like DROSHA, DGCR8, DICER1 and DIS3L2, and alterations in IGF2, MYCN, and TP53, the latter being strongly associated with dismal outcome. DROSHA and DGCR8 mutations had a strong effect on miRNA profiles in tumors, which we confirmed in cell lines transfected with mutant DROSHA.

Study Datasets 4 datasets.

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Dataset ID Description Technology Samples
HIPO blastemal Wilms (nephroblastoma) characterisation of tumor driving events caused by differential SIX1 binding of the SIX1 Q177R mutatns
Illumina HiSeq 2500 3
HIPO blastemal Wilms (nephroblastoma) characterisation of tumor driving gene expression events
Illumina HiSeq 2000 40
HIPO blastemal Wilms (nephroblastoma) characterisation of tumor driving chromosomal aberrations
Illumina HiSeq 2000,Illumina HiSeq 2500 56
HIPO blastemal Wilms (nephroblastoma) characterisation of tumor driving DNA alterations
Illumina HiSeq 2000 112

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