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| Status |
Public on Feb 18, 2015 |
| Title |
Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
|
| Summary |
Blastemal histology in chemotherapy-treated pediatric Wilms tumors (nephroblastoma) is associated with adverse prognosis. To uncover the underlying tumor biology and find novel therapeutic leads for this subgroup of patients, we analyzed 58 blastemal-type Wilms tumors by exome and transcriptome sequencing and validated our findings in a large independent replication cohort. 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 expression patterns in tumors, which was functionally validated in cell lines transfected with mutant DROSHA.
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| Overall design |
total samples analyzed are 16, each done as technical replicate
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| |
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| Contributor(s) |
Vardapour R, Ludwig N, Kneitz S, Gessler M |
| Citation(s) |
25670083 |
| |
| Submission date |
Aug 04, 2014 |
| Last update date |
Jun 07, 2015 |
| Contact name |
Susanne Elma Kneitz |
| E-mail(s) |
susanne.kneitz@uni-wuerzburg.de
|
| Phone |
+49-931-31 86526
|
| Organization name |
University of Wuerzburg
|
| Department |
Physiologigcal Chemistry
|
| Street address |
Biozentrum, Am Hubland
|
| City |
Wuerzburg |
| ZIP/Postal code |
97074 |
| Country |
Germany |
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| Platforms (1) |
| GPL16770 |
Agilent-031181 Unrestricted_Human_miRNA_V16.0_Microarray (miRBase release 16.0 miRNA ID version) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA257428 |
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