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@ARTICLE{Wegert:127763,
author = {J. Wegert and N. Ishaque$^*$ and R. Vardapour and C. Geörg
and Z. Gu$^*$ and M. Bieg$^*$ and B. Ziegler and S.
Bausenwein and N. Nourkami and N. Ludwig and A. Keller and
C. Grimm and S. Kneitz and R. D. Williams and T. Chagtai and
K. Pritchard-Jones and P. van Sluis and R. Volckmann and J.
Koster and R. Versteeg and T. Acha and M. J. O'Sullivan and
P. K. Bode and F. Niggli and G. A. Tytgat and H. van
Tinteren and M. M. van den Heuvel-Eibrink and E. Meese and
C. Vokuhl and I. Leuschner and N. Graf and R. Eils$^*$ and
S. Pfister$^*$ and M. Kool$^*$ and M. Gessler},
title = {{M}utations in the {SIX}1/2 pathway and the
{DROSHA}/{DGCR}8 mi{RNA} microprocessor complex underlie
high-risk blastemal type {W}ilms tumors.},
journal = {Cancer cell},
volume = {27},
number = {2},
issn = {1535-6108},
address = {Cambridge, Mass.},
publisher = {Cell Press},
reportid = {DKFZ-2017-03785},
pages = {298 - 311},
year = {2015},
abstract = {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.},
keywords = {DGCR8 protein, human (NLM Chemicals) / Homeodomain Proteins
(NLM Chemicals) / MicroRNAs (NLM Chemicals) / Neoplasm
Proteins (NLM Chemicals) / Nerve Tissue Proteins (NLM
Chemicals) / RNA-Binding Proteins (NLM Chemicals) / SIX1
protein, human (NLM Chemicals) / SIX2 protein, human (NLM
Chemicals) / DROSHA protein, human (NLM Chemicals) /
Ribonuclease III (NLM Chemicals)},
cin = {B080 / B062},
ddc = {610},
cid = {I:(DE-He78)B080-20160331 / I:(DE-He78)B062-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25670083},
doi = {10.1016/j.ccell.2015.01.002},
url = {https://inrepo02.dkfz.de/record/127763},
}