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Recurrent somatic mutation in DROSHA induces microRNA profile changes in Wilms tumour.
Torrezan, Giovana T; Ferreira, Elisa N; Nakahata, Adriana M; Barros, Bruna D F; Castro, Mayra T M; Correa, Bruna R; Krepischi, Ana C V; Olivieri, Eloisa H R; Cunha, Isabela W; Tabori, Uri; Grundy, Paul E; Costa, Cecilia M L; de Camargo, Beatriz; Galante, Pedro A F; Carraro, Dirce M.
Afiliación
  • Torrezan GT; 1] Genomics and Molecular Biology Laboratory, International Research Center, A. C. Camargo Cancer Center, São Paulo, S.P., 01508-010, Brazil [2].
  • Ferreira EN; 1] Genomics and Molecular Biology Laboratory, International Research Center, A. C. Camargo Cancer Center, São Paulo, S.P., 01508-010, Brazil [2].
  • Nakahata AM; Genomics and Molecular Biology Laboratory, International Research Center, A. C. Camargo Cancer Center, São Paulo, S.P., 01508-010, Brazil.
  • Barros BD; Genomics and Molecular Biology Laboratory, International Research Center, A. C. Camargo Cancer Center, São Paulo, S.P., 01508-010, Brazil.
  • Castro MT; Genomics and Molecular Biology Laboratory, International Research Center, A. C. Camargo Cancer Center, São Paulo, S.P., 01508-010, Brazil.
  • Correa BR; Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, S.P., 01308-060, Brazil.
  • Krepischi AC; Genomics and Molecular Biology Laboratory, International Research Center, A. C. Camargo Cancer Center, São Paulo, S.P., 01508-010, Brazil.
  • Olivieri EH; Genomics and Molecular Biology Laboratory, International Research Center, A. C. Camargo Cancer Center, São Paulo, S.P., 01508-010, Brazil.
  • Cunha IW; Department of Pathology, A. C. Camargo Cancer Center, São Paulo, S.P., 01509-900, Brazil.
  • Tabori U; Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
  • Grundy PE; Cancer Control Alberta, Alberta Health Services, Edmonton, Alberta, Canada AB T5J 3H1.
  • Costa CM; Department of Pediatrics, A. C. Camargo Cancer Center, São Paulo, S.P., 01509-010, Brazil.
  • de Camargo B; Pediatric Hematology-Oncology Research Program, Instituto Nacional de Cancer, INCA, Rio de Janeiro, R.J., 20231-050, Brazil.
  • Galante PA; Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, S.P., 01308-060, Brazil.
  • Carraro DM; Genomics and Molecular Biology Laboratory, International Research Center, A. C. Camargo Cancer Center, São Paulo, S.P., 01508-010, Brazil.
Nat Commun ; 5: 4039, 2014 Jun 09.
Article en En | MEDLINE | ID: mdl-24909261
Wilms tumour (WT) is an embryonal kidney neoplasia for which very few driver genes have been identified. Here we identify DROSHA mutations in 12% of WT samples (26/222) using whole-exome sequencing and targeted sequencing of 10 microRNA (miRNA)-processing genes. A recurrent mutation (E1147K) affecting a metal-binding residue of the RNase IIIb domain is detected in 81% of the DROSHA-mutated tumours. In addition, we identify non-recurrent mutations in other genes of this pathway (DGCR8, DICER1, XPO5 and TARBP2). By assessing the miRNA expression pattern of the DROSHA-E1147K-mutated tumours and cell lines expressing this mutation, we determine that this variant leads to a predominant downregulation of a subset of miRNAs. We confirm that the downregulation occurs exclusively in mature miRNAs and not in primary miRNA transcripts, suggesting that the DROSHA E1147K mutation affects processing of primary miRNAs. Our data underscore the pivotal role of the miRNA biogenesis pathway in WT tumorigenesis, particularly the major miRNA-processing gene DROSHA.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tumor de Wilms / MicroARNs / Ribonucleasa III / Mutación Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2014 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tumor de Wilms / MicroARNs / Ribonucleasa III / Mutación Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2014 Tipo del documento: Article Pais de publicación: Reino Unido