da Silveira Michele Amaral, Ferreira Wallax Augusto Silva, Amorim Carolina Koury Nassar, Brito José Reginaldo Nascimento, Kayath André Salim, Sagica Fernanda do Espirito Santo, de Oliveira Edivaldo Herculano Corrêa
Programa de Pós-Graduação em Neurociências e Biologia Celular, ICB, UFPA, Rua Augusto Correa, 01, Belém, PA 66075-990, Brazil.
Laboratório de Cultura de Tecidos e Citogenética, Seção de Meio Ambiente, Instituto Evandro Chagas, BR 316 Km 7, s/n Levilândia, Ananindeua, PA, Brazil.
J Oncol. 2020 Jun 29;2020:3821695. doi: 10.1155/2020/3821695. eCollection 2020.
Meningiomas are considered the most common intracranial tumors, affecting mainly women. Studies in mixed populations can be of great importance to clarify issues related to the genetic diversity of tumors and their development. Considering that data obtained from analyses of the profile of copy number alterations (CNA) have been a useful diagnostic indicator for many types of tumors and that meningiomas show a complex pattern of gains and losses in the number of copies, our objective was to analyze the CNA profile in 33 samples of meningiomas of different histological grades (WHO Grade I-III) from patients in a city located in the Amazon region of Brazil, using aCGH. We found that the female to male ratio was 3 : 1. The aCGH analysis revealed a total of 2304 CNA, with an average of 69.8 ± 57.4 per case, of which 1197 were gains (52%), 926 were losses (40.2%), 105 were amplifications (4. 5%), and 76 were deletions (3.3%). A significant relationship was observed between the type of CNA and the degree of the tumor (chi-square test: = 65,844; < 0.0001; contingency coefficient: = 0.1772; < 0.0001). Evaluating the recurrent changes in at least 50% of the samples, we observe as the most frequent losses of the segments 22q13.1-q13.2 (82%), 1p35.3 (76%), and 14q13.1-q13.2 (67%), involving all histopathological grades. The analysis of these regions showed the inclusion of genes with functions such as regulation, maintenance of cell survival, reorganization of the cytoskeleton, cell signaling, and DNA repair, among others. However, overall, the profiles observed in meningiomas of this admixed population were very similar to the ones observed in Caucasian groups. An interesting finding was a recurrent gain of 8p22 observed only in grade I meningiomas, a region which includes DLC1, a suppressor candidate gene probably implicated in the developments or progression of meningiomas, usually found deleted, when related to CNAs.
脑膜瘤被认为是最常见的颅内肿瘤,主要影响女性。对混合人群的研究对于阐明与肿瘤遗传多样性及其发展相关的问题可能非常重要。鉴于从拷贝数改变(CNA)谱分析中获得的数据已成为多种肿瘤的有用诊断指标,且脑膜瘤在拷贝数上呈现出复杂的增减模式,我们的目标是使用aCGH分析巴西亚马逊地区一个城市患者的33例不同组织学分级(世界卫生组织I - III级)脑膜瘤样本的CNA谱。我们发现女性与男性的比例为3∶1。aCGH分析共发现2304个CNA,平均每例69.8±57.4个,其中1197个为增加(52%),926个为减少(40.2%),105个为扩增(4.5%),76个为缺失(3.3%)。观察到CNA类型与肿瘤分级之间存在显著关系(卡方检验:χ² = 65.844;P < 0.0001;列联系数:C = 0.1772;P < 0.0001)。评估至少50%样本中的复发变化,我们观察到最常见的是22q13.1 - q13.2(82%)、1p35.3(76%)和14q13.1 - q13.2(67%)片段的缺失,涉及所有组织病理学分级。对这些区域的分析显示包含了具有调控、维持细胞存活、细胞骨架重组、细胞信号传导和DNA修复等功能的基因。然而,总体而言,在这个混合人群的脑膜瘤中观察到的谱与在白种人群体中观察到的非常相似。一个有趣的发现是仅在I级脑膜瘤中观察到8p22的复发增加,该区域包含DLC1,一个可能与脑膜瘤的发生或进展有关的候选抑癌基因,在与CNA相关时通常发现缺失。