G.R. Pinto1,2, C.A. Clara3,
M.J. Santos3, J.R.W. Almeida3, R.R. Burbano4,
J.A. Rey5 and
C. Casartelli2
1Laboratório de Genética Humana
e Biologia Molecular,
Universidade Federal do Piauí, Parnaíba, PI, Brasil
2Laboratório de Oncogenética, Departamento de
Genética,
Faculdade de Medicina de Ribeirão Preto, Universidade de São
Paulo,
Ribeirão Preto, SP, Brasil
3Fundação Pio XII, Hospital de Câncer de
Barretos, Barretos, SP, Brasil
4Laboratório de Citogenética Humana e Genética
Toxicológica,
Departamento de Biologia, Universidade Federal do Pará, Belém,
PA, Brasil
5Laboratorio de Oncogenética Molecular,
Departamento de Cirugía Experimental, Hospital Universitario La
Paz, Madrid, Spain
Corresponding author: G.R. Pinto
E-mail: pintogr@gmail.com
Genet. Mol. Res. 6 (4): 1019-1025 (2007)
Received June 29, 2007
Accepted September 30, 2007
Published November 27, 2007
ABSTRACT. Gliomas are the most common tumors of the central nervous system. In spite of the marked advances in the characterization of the molecular pathogenesis of gliomas, these tumors remain incurable and, in most of the cases, resistant to treatments, due to their molecular heterogeneity. Gene PAX6, which encodes a transcription factor that plays an important role in the development of the central nervous system, was recently recognized as a tumor suppressor in gliomas. The objective of the present study was to analyze the mutational status of the coding and regulating regions of PAX6 in 94 gliomas: 81 astrocytomas (11 grade I, 23 grade II, 8 grade III, and 39 grade IV glioblastomas), 5 oligodendrogliomas (3 grade II, and 2 grade III), and 8 ependymomas (5 grade II, and 3 grade III). Two regulating regions (SX250 and EIE) and the 11 coding regions (exons 4-13, plus exon 5a resulting from alternative splicing) of gene PAX6 were analyzed and no mutation was found. Therefore, we conclude that the tumor suppressor role of PAX6, reported in previous studies on gliomas, is not due to mutation in its coding and regulating regions, suggesting the involvement of epigenetic mechanisms in the silencing of PAX6 in these tumors.
Key words: Mutation, PAX6, Gliomas