作者
Jenny Wegert, Naveed Ishaque, Romina Vardapour, Christina Geörg, Zuguang Gu, Matthias Bieg, Barbara Ziegler, Sabrina Bausenwein, Nasenien Nourkami, Nicole Ludwig, Andreas Keller, Clemens Grimm, Susanne Kneitz, Richard D Williams, Tas Chagtai, Kathy Pritchard-Jones, Peter van Sluis, Richard Volckmann, Jan Koster, Rogier Versteeg, Tomas Acha, Maureen J O’Sullivan, Peter K Bode, Felix Niggli, Godelieve A Tytgat, Harm van Tinteren, Marry M van den Heuvel-Eibrink, Eckart Meese, Christian Vokuhl, Ivo Leuschner, Norbert Graf, Roland Eils, Stefan M Pfister, Marcel Kool, Manfred Gessler
发表日期
2015/2/9
期刊
Cancer cell
卷号
27
期号
2
页码范围
298-311
出版商
Elsevier
简介
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.
学术搜索中的文章
J Wegert, N Ishaque, R Vardapour, C Geörg, Z Gu… - Cancer cell, 2015