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

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

Author Cordeiro, Bruna Mascaro Autor UNIFESP Google Scholar
Oliveira, Indhira Dias Autor UNIFESP Google Scholar
Seixas Alves, Maria Teresa de Autor UNIFESP Google Scholar
Saba-Silva, Nasjla Autor UNIFESP Google Scholar
Capellano, Andrea M. Autor UNIFESP Google Scholar
Cavalheiro, Sergio Autor UNIFESP Google Scholar
Dastoli, Patricia Autor UNIFESP Google Scholar
Toledo, Silvia Regina Caminada de Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract 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.
Keywords Medulloblastoma
WNT
SHH
NOTCH
Gene expression
Molecular targets
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grupo de Apoio ao Adolescente e Criança com Câncer (GRAACC)
Grant number FAPESP: 2011/19629-0
FAPESP: 2011/16221-0
Date 2014-07-01
Published in Childs Nervous System. New York: Springer, v. 30, n. 7, p. 1165-1172, 2014.
ISSN 0256-7040 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 1165-1172
Origin http://dx.doi.org/10.1007/s00381-014-2403-x
Access rights Closed access
Type Article
Web of Science ID WOS:000338631100005
URI http://repositorio.unifesp.br/handle/11600/37924

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