SHH, WNT, and NOTCH pathways in medulloblastoma: when cancer stem cells maintain self-renewal and differentiation properties

Autor(es)

Cordeiro, Bruna Mascaro ^{[1, 2]} ; Oliveira, Indhira Dias ^{[1, 2]} ; de Seixas Alves, Maria Teresa ^{[3, 1]} ; Saba-Silva, Nasjla ^[1] ; Capellano, Andrea M. ^[1] ; Cavalheiro, Sergio ^{[1, 4]} ; Dastoli, Patricia ^[1] ; Caminada Toledo, Silvia Regina ^{[1, 2, 5]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Pediat Oncol Inst, GRAACC, Dept Pediat, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Morphol & Genet, Div Genet, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Pathol, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Dept Neurol, Sao Paulo - Brazil

^[5] UNIFESP Fed Univ Sao Paulo, GRAACC Grp Apoio Adolescente & Crianca Canc, Pediat Oncol Inst, Genet Lab, BR-04023062 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CHILD'S NERVOUS SYSTEM; v. 30, n. 7, p. 1165-1172, JUL 2014.
• Citações Web of Science: 17

Resumo

Infant medulloblastoma (MB) is a malignant neuroepithelial embryonal tumor of the cerebellum, believed to derive from precursor granule cells with stem or progenitor cells appearance, and caused by a change in expression profile of genes related to the development. This work aims to study the expression profile of these genes in MB tumors, correlating with clinicopathological characteristics. We quantified, by qPCR in 40 MB tumor samples, the expression of genes in HH (PTCH1, PTCH2, and GLI1), WNT (APC, CTNNB1, WIF1, and DKK2), and NOTCH pathways (NOTCH2 and HES1), which have a crucial role in development, and genes as MYCC, MYCN, and TERT, correlating this findings to patient's clinicopathological characteristics. Considering the universal RNA as our control sample, and considering the median of gene expression in the control samples as our cutoff, we observed that HES1 gene showed decreased expression compared to control (p = 0.0059), but patients with HES1 overexpression were directly related to a shorter survival (p = 0.0165). Individuals with higher GLI1 gene expression had significant shorter survival (p = 0.0469), and high expression was prevalent in patients up to 5 years old (p = 0.0479). Patients showing high PTCH2 expression were related to worse survival (p = 0.0426), and it was correlated with GLI1 high expression (p = 0.0094). We also observed a concomitant overexpression of WIF1 and DKK2 genes in a subgroup of MB samples (n = 11, p = 0.0118). Our results suggest the presence of activated developmental signaling pathways in MB, which are important for cell proliferation and maintenance, and that may be targeted for novel therapeutic options. (AU)

• Processo FAPESP: 11/19629-0 - Investigação de marcadores prognóstico na evolução dos tumores do sistema nervoso central mais frequentes da infância e adolescência: astrocitoma pilocítico e meduloblastoma
• Beneficiário: Silvia Regina Caminada de Toledo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/16221-0 - Análise da expressão de genes de desenvolvimento no meduloblastoma e sua relação com a evolução clínica dos pacientes
• Beneficiário: Bruna Mascaro Cordeiro de Azevedo
• Modalidade de apoio: Bolsas no Brasil - Mestrado