Jesus-Ribeiro Joana, Rebelo Olinda, Ribeiro Ilda Patrícia, Pires Luís Miguel, Melo João Daniel, Sales Francisco, Santana Isabel, Freire António, Melo Joana Barbosa
Neurology Department, Centro Hospitalar de Leiria, Leiria, Portugal.
Coimbra Institute for Clinical and Biomedical Research (iCBR) and Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Neuropathology. 2022 Dec;42(6):467-482. doi: 10.1111/neup.12846. Epub 2022 Jul 17.
Low-grade neuroepithelial tumors (LNETs) represent an important group of central nervous system neoplasms, some of which may be associated to epilepsy. The concept of long-term epilepsy-associated tumors (LEATs) includes a heterogenous group of low-grade, cortically based tumors, associated to drug-resistant epilepsy, often requiring surgical treatment. LEATs entities can sometimes be poorly discriminated by histological features, precluding a confident classification in the absence of additional diagnostic tools. This study aimed to provide an updated review on the genomic findings and DNA methylation profiling advances in LNETs, including histological entities of LEATs. A comprehensive search strategy was conducted on PubMed, Embase, and Web of Science Core Collection. High-quality peer-reviewed original manuscripts and review articles with full-text in English, published between 2003 and 2022, were included. Results were screened based on titles and abstracts to determine suitability for inclusion, and when addressed the topic of the review was screened by full-text reading. Data extraction was performed through a qualitative content analysis approach. Most LNETs appear to be driven mainly by a single genomic abnormality and respective affected signaling pathway, including BRAF p.V600E mutations in ganglioglioma, FGFR1 abnormalities in dysembryoplastic neuroepithelial tumor, MYB alterations in angiocentric glioma, BRAF fusions in pilocytic astrocytoma, PRKCA fusions in papillary glioneuronal tumor, between others. However, these molecular alterations are not exclusive, with some overlap amongst different tumor histologies. Also, clustering analysis of DNA methylation profiles allowed the identification of biologically similar molecular groups that sometimes transcend conventional histopathological classification. The exciting developments on the molecular basis of these tumors reinforce the importance of an integrative histopathological and (epi)genetic classification, which can be translated into precision medicine approaches.
低级别神经上皮肿瘤（LNETs）是中枢神经系统肿瘤的一个重要类别，其中一些可能与癫痫有关。长期癫痫相关肿瘤（LEATs）的概念包括一组异质性的、位于皮质的低级别肿瘤，与药物难治性癫痫相关，通常需要手术治疗。LEATs实体有时在组织学特征上难以区分，在缺乏其他诊断工具的情况下难以进行可靠分类。本研究旨在对LNETs的基因组学发现和DNA甲基化谱分析进展进行更新综述，包括LEATs的组织学实体。我们在PubMed、Embase和Web of Science核心合集上进行了全面的检索策略。纳入了2003年至2022年间发表的高质量、经过同行评审的英文全文原创手稿和综述文章。根据标题和摘要筛选结果以确定是否适合纳入，当涉及综述主题时通过全文阅读进行筛选。通过定性内容分析方法进行数据提取。大多数LNETs似乎主要由单一的基因组异常和相应受影响的信号通路驱动，包括神经节细胞胶质瘤中的BRAF p.V600E突变、胚胎发育不良性神经上皮肿瘤中的FGFR1异常、血管中心性胶质瘤中的MYB改变、毛细胞型星形细胞瘤中的BRAF融合、乳头状胶质神经元肿瘤中的PRKCA融合等。然而，这些分子改变并非排他性的，不同肿瘤组织学之间存在一些重叠。此外，DNA甲基化谱的聚类分析能够识别出有时超越传统组织病理学分类的生物学上相似的分子组。这些肿瘤分子基础方面令人兴奋的进展强化了综合组织病理学和（表观）遗传学分类的重要性，这可以转化为精准医学方法。
