Valentin Mev Dominguez, Canalle Renata, Queiroz Rosane de Paula, Tone Luiz Gonzaga
Genomic and Molecular Laboratory, Research Center, Hospital A. C. Camargo, São Paulo, Brazil.
Sao Paulo Med J. 2009 Sep;127(5):288-94. doi: 10.1590/s1516-31802009000500008.
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.
中枢神经系统（CNS）肿瘤的遗传学研究为调控中枢神经系统增殖、分化、血管生成、迁移及凋亡的基因提供了有价值的信息。本研究旨在确定细胞周期蛋白依赖性激酶抑制剂1A（CDKN1A）基因的遗传多态性（密码子31和3'非翻译区，3'UTR）及蛋白表达在中枢神经系统肿瘤患者和非肿瘤患者中的发生率。
在里贝朗普雷图临床医院儿科肿瘤科分子生物学实验室进行的有对照组的分析性横断面研究。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术对41例中枢神经系统肿瘤患者及161例无癌症的对照组受试者（按性别、年龄和种族配对）进行基因分型。使用蛋白质印迹技术对36例中枢神经系统肿瘤患者进行蛋白分析。
对照组中密码子31杂合子（Ser/Arg）和多态性纯合子（Arg/Arg）基因型的频率分别为28.0%和1.2%。然而，3'UTR位点的频率分别为24.2%（C/T）和0.6%（T/T）。这些频率与中枢神经系统肿瘤患者（密码子31为19.4%和0.0%；3'UTR位点为15.8%和2.6%）相比无统计学差异（P>0.05）。关于室管膜瘤中的蛋白表达，66.67%未表达CDKN1A蛋白。髓母细胞瘤和星形细胞瘤的结果相似：两者均未表达该蛋白（分别为57.14%和61.54%）。
在巴西受试者中，未观察到CDKN1A蛋白表达模式或多态性与三种类型中枢神经系统肿瘤之间存在显著差异。
