Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors
Copyright © 2015 Elsevier Inc. All rights reserved..
Blastemal histology in chemotherapy-treated pediatric Wilms tumors (nephroblastoma) is associated with adverse prognosis. To uncover the underlying tumor biology and find therapeutic leads for this subgroup, we analyzed 58 blastemal type Wilms tumors by exome and transcriptome sequencing and validated our findings in a large replication cohort. Recurrent mutations included a hotspot mutation (Q177R) in the homeo-domain of SIX1 and SIX2 in tumors with high proliferative potential (18.1% of blastemal cases); mutations in the DROSHA/DGCR8 microprocessor genes (18.2% of blastemal cases); mutations in DICER1 and DIS3L2; and alterations in IGF2, MYCN, and TP53, the latter being strongly associated with dismal outcome. DROSHA and DGCR8 mutations strongly altered miRNA expression patterns in tumors, which was functionally validated in cell lines expressing mutant DROSHA.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Cancer cell - 27(2015), 2 vom: 09. Feb., Seite 298-311 |
| Sprache: |
Englisch |
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| Links: |
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| Anmerkungen: |
Date Completed 24.04.2015 Date Revised 10.02.2024 published: Print GEO: GSE53224, GSE57370, GSE60081 Citation Status MEDLINE |
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| doi: |
10.1016/j.ccell.2015.01.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM246126671 |
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| 100 | 1 | |a Wegert, Jenny |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors |
| 264 | 1 | |c 2015 | |
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| 500 | |a Date Completed 24.04.2015 | ||
| 500 | |a Date Revised 10.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a GEO: GSE53224, GSE57370, GSE60081 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2015 Elsevier Inc. All rights reserved. | ||
| 520 | |a Blastemal histology in chemotherapy-treated pediatric Wilms tumors (nephroblastoma) is associated with adverse prognosis. To uncover the underlying tumor biology and find therapeutic leads for this subgroup, we analyzed 58 blastemal type Wilms tumors by exome and transcriptome sequencing and validated our findings in a large replication cohort. Recurrent mutations included a hotspot mutation (Q177R) in the homeo-domain of SIX1 and SIX2 in tumors with high proliferative potential (18.1% of blastemal cases); mutations in the DROSHA/DGCR8 microprocessor genes (18.2% of blastemal cases); mutations in DICER1 and DIS3L2; and alterations in IGF2, MYCN, and TP53, the latter being strongly associated with dismal outcome. DROSHA and DGCR8 mutations strongly altered miRNA expression patterns in tumors, which was functionally validated in cell lines expressing mutant DROSHA | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a DGCR8 protein, human |2 NLM | |
| 650 | 7 | |a Homeodomain Proteins |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a Neoplasm Proteins |2 NLM | |
| 650 | 7 | |a Nerve Tissue Proteins |2 NLM | |
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| 700 | 1 | |a Vardapour, Romina |e verfasserin |4 aut | |
| 700 | 1 | |a Geörg, Christina |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Zuguang |e verfasserin |4 aut | |
| 700 | 1 | |a Bieg, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Ziegler, Barbara |e verfasserin |4 aut | |
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| 700 | 1 | |a Williams, Richard D |e verfasserin |4 aut | |
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