Gene expression analysis of blastemal component reveals genes associated with relapse mechanism in Wilms tumour

Autor(es)

Maschietto, Mariana ^[1] ; Piccoli, Fabio S. ^[1] ; Costa, Cecilia M. L. ^[2] ; Camargo, Luiz P. ^[3] ; Neves, Jose I. ^[4] ; Grundy, Paul E. ^[5] ; Brentani, Helena ^[3] ; Soares, Fernando A. ^[5] ; de Camargo, Beatriz ; Carraro, Dirce M. ^[1]

Afiliação do(s) autor(es)

^[1] Hosp AC Camargo Fund Antonio Prudente, Lab Genom & Mol Biol, CIPE, BR-01509010 Sao Paulo - Brazil

^[2] Hosp AC Camargo Fund Antonio Prudente, Dept Pediat, BR-01509010 Sao Paulo - Brazil

^[3] Hosp AC Camargo Fund Antonio Prudente, Lab Bioinformat, CIPE, BR-01509010 Sao Paulo - Brazil

^[4] Hosp AC Camargo Fund Antonio Prudente, Dept Anat Pathol, BR-01509010 Sao Paulo - Brazil

^[5] Stollery Childrens Hosp, Edmonton, AB - Canada

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF CANCER; v. 47, n. 18, p. 2715-2722, DEC 2011.
• Citações Web of Science: 13

Resumo

Wilms tumour (WT) is a paediatric kidney tumour, composed of blastemal, epithelial and stromal cells, with a relapse rate of approximately 15%. Long-term survival for patients with relapse remains approximately 50%. Current clinical and molecular research is directed towards identifying prognostic factors to define the minimal and intensive therapy for successful treatment of children with low and high risk of relapse, respectively. Blastemal component presents a high level of aggressiveness and responsiveness to chemotherapy. To identify molecular prognostic markers that are predictive of chemotherapy sensitivity in tumour relapse, blastemal-enriched samples from stage III and IV WT, from patients with relapse or without relapse, were analysed for 4608 human genes immobilised on a customised cDNA platform. These analyses revealed 69 differentially expressed genes, and the top nine genes were further evaluated by qRT-PCR in the initial WT samples. TSPAN3, NCOA6, CDO1, MPP2 and MCM2 were confirmed to be down-regulated in relapse WT, and TSPAN3 and NCOA6 were also validated in an independent sample group. Protein expression of MCM2 and NCOA6 were observed in 38% (13 out of 34) and 28% (9 out of 32), respectively, of independent stage III and IV WT blastema samples, without association with relapse. However, a significant association between MCM2 positive staining and chemotherapy as first treatment suggests the involvement of MCM2 with drug metabolism in WT blastemal cells. (C) 2011 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 98/14335-2 - Antonio Prudente Cancer Research Center
• Beneficiário: Fernando Augusto Soares
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 06/00054-0 - Análise de expressão gênica de vários estágios de desenvolvimento do rim e fígado e suas implicações em tumores embrionários
• Beneficiário: Dirce Maria Carraro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/00081-7 - Caracterizacao da expressao dos genes da via de sinalizacao wnt e do processo de transicao epitelio-mesenquima durante a embriogenese de rim e figado e suas implicacoes em tumores embrionarios.
• Beneficiário: Mariana Camargo Maschietto
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 05/05184-6 - Identificação de potenciais marcadores de resposta terapêutica para o tumor de Wilms através do microarray usando plataforma de cDNA contendo genes pertencentes à via do ácido retinóico
• Beneficiário: Fábio de Simone Piccoli
• Modalidade de apoio: Bolsas no Brasil - Doutorado