Abstract
Genetic investigation of central nervous system (CNS) tumors provides valuable information about the genes regulating proliferation, differentiation, angiogenesis, migration and apoptosis in the CNS. The aim of our study was to determine the prevalence of genetic polymorphisms (codon 31 and 3' untranslated region, 3'UTR) and protein expression of the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene in patients with and without CNS tumors. Analytical cross-sectional study with a control group, at the Molecular Biology Laboratory, Pediatric Oncology Department, Hospital das Clínicas de Ribeirão Preto. 41 patients with CNS tumors and a control group of 161 subjects without cancer and paires for sex, age and ethnicity were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Protein analysis was performed on 36 patients with CNS tumors, using the Western Blotting technique. The frequencies of the heterozygote (Ser/Arg) and polymorphic homozygote (Arg/Arg) genotypes of codon 31 in the control subjects were 28.0% and 1.2%, respectively. However, the 3'UTR site presented frequencies of 24.2% (C/T) and 0.6% (T/T). These frequencies were not statistically different (P > 0.05) from those seen in the patients with CNS tumors (19.4% and 0.0%, codon 31; 15.8% and 2.6%, 3'UTR site). Regarding the protein expression in ependymomas, 66.67% did not express the protein CDKN1A. The results for medulloblastomas and astrocytomas were similar: neither of them expressed the protein (57.14% and 61.54%, respectively). No significant differences in protein expression patterns or polymorphisms of CDKN1A in relation to the three types of CNS tumors were observed among Brazilian subjects.
Highlights
Central nervous system (CNS) tumors are the second most common type of pediatric cancer, exceeded only by leukemia, and they are the most common solid tumor during childhood
This tissue came from patients younger than 18 years of age who were treated for medulloblastoma (n = 16), ependymoma (n = 10) and astrocytoma (n = 15) in the Pediatric Oncology and Hematology Department and the Neurosurgery Department of Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HC-FMRP-Universidade de São Paulo (USP))
Among the 36 CNS tumor patients studied for the polymorphism in codon 31, none of them (0.0%) presented the transversion codon transversion (C→A) in codon 31
Summary
Central nervous system (CNS) tumors are the second most common type of pediatric cancer, exceeded only by leukemia, and they are the most common solid tumor during childhood. The etiology of brain and CNS tumors is largely unknown, genetic investigation of CNS tumors provides valuable information about the genes regulating proliferation, differentiation, angiogenesis, migration and apoptosis in the CNS. CDKN1A may lead to differentiation of normal and transformed cells and suppression of malignant cell growth in vitro and in vivo.[2] it may lead to apoptosis involving the tumor protein 53 (TP53) and retinoblastoma protein (RB) signaling pathways, in the same way as in senescence.[3] Changes in the CDKN1A gene and its expression may have an important role in cancer pathogenesis, since its normal function comprises suspension of the cell cycle, terminal differentiation and apoptosis. Different types of neoplasms correlate with CDKN1A abnormalities, including cervical neoplasms, colorectal carcinoma, ovary carcinoma, bladder cancer, prostate cancer, hepatomas and others.[4,5,6,7,8]
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