| Literature DB >> 25670083 |
Jenny Wegert1, Naveed Ishaque2, Romina Vardapour1, Christina Geörg3, Zuguang Gu2, Matthias Bieg2, Barbara Ziegler1, Sabrina Bausenwein1, Nasenien Nourkami4, Nicole Ludwig5, Andreas Keller5, Clemens Grimm6, Susanne Kneitz7, Richard D Williams8, Tas Chagtai8, Kathy Pritchard-Jones8, Peter van Sluis9, Richard Volckmann9, Jan Koster9, Rogier Versteeg9, Tomas Acha10, Maureen J O'Sullivan11, Peter K Bode12, Felix Niggli12, Godelieve A Tytgat13, Harm van Tinteren13, Marry M van den Heuvel-Eibrink14, Eckart Meese5, Christian Vokuhl15, Ivo Leuschner15, Norbert Graf4, Roland Eils16, Stefan M Pfister17, Marcel Kool17, Manfred Gessler18.
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.Entities:
Mesh：
Substances：
Year: 2015 PMID： 25670083 DOI： 10.1016/j.ccell.2015.01.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743