Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors.

TitleRecurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors.
Publication TypeJournal Article
Year of Publication2015
AuthorsWalz, AL, Ooms, A, Gadd, S, Gerhard, DS, Smith, MA, Auvil, JMGuidry, Meerzaman, D, Chen, Q-R, Hsu, CHao, Yan, C, Nguyen, C, Hu, Y, Bowlby, R, Brooks, D, Ma, Y, Mungall, AJ, Moore, RA, Schein, J, Marra, MA, Huff, V, Dome, JS, Chi, Y-Y, Mullighan, CG, Ma, J, Wheeler, DA, Hampton, OA, Jafari, N, Ross, N, Gastier-Foster, JM, Perlman, EJ
JournalCancer Cell
Volume27
Issue2
Pagination286-97
Date Published2015 Feb 09
ISSN1878-3686
KeywordsGene Expression Regulation, Neoplastic, Homeodomain Proteins, Humans, Loss of Heterozygosity, MicroRNAs, Mutation, Neoplasm Recurrence, Local, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Ribonuclease III, RNA-Binding Proteins, Wilms Tumor
Abstract

We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations. Significantly decreased expression of mature Let-7a and the miR-200 family (responsible for mesenchymal-to-epithelial transition) in miRNAPG mutant tumors is associated with an undifferentiated blastemal histology. The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death.

DOI10.1016/j.ccell.2015.01.003
Alternate JournalCancer Cell
PubMed ID25670082
PubMed Central IDPMC4800737
Grant ListT32 CA079447 / CA / NCI NIH HHS / United States
U10CA98543 / CA / NCI NIH HHS / United States
U24 CA114766 / CA / NCI NIH HHS / United States
U10CA42326 / CA / NCI NIH HHS / United States
U01 CA088131 / CA / NCI NIH HHS / United States
U10 CA098543 / CA / NCI NIH HHS / United States
HHSN261200800001C / RC / CCR NIH HHS / United States
UO1CA88131 / CA / NCI NIH HHS / United States
U10 CA180886 / CA / NCI NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States
U10 CA98543 / CA / NCI NIH HHS / United States

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