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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 5
Document type: Journal article
Source: CHILD'S NERVOUS SYSTEM; v. 30, n. 7, p. 1165-1172, JUL 2014.
Web of Science Citations: 17
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. (AU)

FAPESP's process: 11/19629-0 - Prognostic markers investigation in brain tumors most frequenttly in childhood and adolescents: pilocytic astrocytoma and medulloblastoma
Grantee:Silvia Regina Caminada de Toledo
Support Opportunities: Regular Research Grants
FAPESP's process: 11/16221-0 - Analysis of gene expression profile in medulloblastoma development and its relationship to patients clinical outcome
Grantee:Bruna Mascaro Cordeiro de Azevedo
Support Opportunities: Scholarships in Brazil - Master