Prognostic markers investigation in brain tumors most frequenttly in childhood and adolescents: pilocytic astrocytoma and medulloblastoma

• Grant number: 11/19629-0
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2012
• End date: December 31, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Silvia Regina Caminada de Toledo
• Grantee: Silvia Regina Caminada de Toledo
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Andrea Maria Cappellano ; Nasjla Saba da Silva ; Sergio Cavalheiro

Abstract

Gliomas are epithelial tumors derived mainly from astrocytes. The low-grade tumors comprise the majority of these cancers in children, while high-grade, especially glioblastoma multiforme, are prevalent in adults. Little is known about the molecular characteristics of low-grade gliomas of childhood, and the genetic alterations observed frequently in adult tumors are rarely found in this age group. Studies show that 80% of pilocytic astrocytomas from pediatric patients had a fusion gene KIAA1549-BRAF, but this fusion gene was rarely found in diffuse astrocytomas. Identification of the BRAF gene fusion can be used to distinguish between pilocytic astrocytomas and grade II astrocytomas, since this distinction can be difficult based only on histopathology. Medulloblastoma (MB) is an embryonal neuroepithelial tumor that represents about 16 to 25% of all central nervous system tumors of childhood. Resistance to treatment and tumor recurrence is often associated with the presence of tumor stem cells, and these are determinants of poor prognosis. Like stem cells, tumor stem cells are considered able to proliferate indefinitely, a capability that is caused by dysregulation of key signaling pathways which plays a key role in development, such as Hedgehog (Hh ), Wnt and Notch pathways. Recent studies have revealed that the prognosis and treatment of MB depends on the origin of tumor cells, genes and pathways involved in activation and deactivation of these cells. Thus, current targeted therapies have been based on small molecules for specific signaling pathways altered in the oncogenic process of MB. Once the central nervous system tumors are the second most common type of cancer in children and adolescents, any investigation that will enable a better understanding of the process and the adequacy of tumor treatment, which now also increases the morbidity of these patients, is justified. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CORDEIRO, BRUNA MASCARO; OLIVEIRA, INDHIRA DIAS; DE SEIXAS ALVES, MARIA TERESA; SABA-SILVA, NASJLA; CAPELLANO, ANDREA M.; CAVALHEIRO, SERGIO; DASTOLI, PATRICIA; CAMINADA TOLEDO, SILVIA REGINA. SHH, WNT, and NOTCH pathways in medulloblastoma: when cancer stem cells maintain self-renewal and differentiation properties. CHILD'S NERVOUS SYSTEM, v. 30, n. 7, p. 1165-1172, JUL 2014. (11/19629-0, 11/16221-0)

CRUZ, GABRIELA RAMPAZZO; OLIVEIRA, INDHIRA DIAS; MORAES, LAIS; PANIAGO, MARIO DEL GIUDICE; DE SEIXAS ALVES, MARIA TERESA; CAPELLANO, ANDREA MARIA; SABA-SILVA, NASJLA; CAVALHEIRO, SERGIO; CERUTTI, JANETE MARIA; CAMINADA TOLEDO, SILVIA REGINA. Analysis of KIAA1549-BRAF fusion gene expression and IDH1/IDH2 mutations in low grade pediatric astrocytomas. JOURNAL OF NEURO-ONCOLOGY, v. 117, n. 2, p. 235-242, APR 2014. (11/19629-0, 11/16221-0)