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|
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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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|