Canine meningiomas are comprised of 3 DNA methylation groups that resemble the molecular characteristics of human meningiomas.
Canine meningiomas are comprised of 3 DNA methylation groups that resemble the molecular characteristics of human meningiomas.
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犬脑膜瘤由 3 个 DNA 甲基化基团组成，类似于人类脑膜瘤的分子特征。
DOI：
10.1007/s00401-024-02693-2
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发表时间：
2024
影响因子：
12.7
通讯作者：
Raleigh,DavidR
中科院分区：
文献类型：
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作者：
Zakimi,Naomi;Mazcko,ChristinaN;Toedebusch,Christine;Tawa,Gregory;Woolard,Kevin;LeBlanc,AmyK;Dickinson,PeterJ;Raleigh,DavidR
脑膜瘤是人类[16]和狗[18，20]最常见的原发颅内肿瘤。对人类脑膜瘤的DNA甲基化或RNA测序数据的非监督分析揭示了与不同的生物驱动因素、治疗脆弱性和临床结果相关的三个肿瘤分子组[5，17]。这些共识的分子群与拷贝数变异(CNV)、DNA甲基化图谱、RNA测序数据和体细胞短变异的综合聚类分析结果一致，这表明人类脑膜瘤的分子群可以由亚群组成[4，15]。在这里，我们测试了这样一个假设，即对犬脑膜瘤分子特征的比较了解可能有助于阐明这些自然发生的肿瘤作为人类脑膜瘤模型的可治性[9]，考虑到脑膜瘤基因工程小鼠模型的局限性，这一知识可能特别有用[6]。全基因组二硫化物测序(WGBS)对29个犬脑膜瘤进行了研究，这些脑膜瘤横跨所有组织学级别，不同的颅内和脊髓位置，以及23个品种的狗(补充表1)。大多数犬脑膜瘤具有脑膜上皮或微囊结构，为CNS WHO 1级(29个肿瘤中有19个)，但
Meningiomas are the most common primary intracranial tumor in humans [16] and in dogs [18, 20]. Unsupervised analyses of DNA methylation or RNA sequencing data from human meningiomas reveal three molecular groups of tumors that are associated with distinct biological drivers, therapeutic vulnerabilities, and clinical outcomes [5, 17]. These consensus molecular groups are concordant with results of integrated clustering analyses of copy number variants (CNVs), DNA methylation profiles, RNA sequencing data, and somatic short variants, which suggest that molecular groups of human meningiomas can be comprised of subgroups [4, 15]. Here we test the hypothesis that comparative understanding of the molecular characteristics of canine meningiomas may shed light on the tractability of these naturally occurring tumors as models for meningiomas in humans [9], knowledge that might be particularly useful given the limitations of genetically engineered mouse models of meningioma [6].Whole genome bisulfide sequencing (WGBS) was performed on 29 canine meningiomas spanning all histological grades, a diversity of intracranial and spinal locations, and 23 breeds of dogs (Supplementary Table 1). Most canine meningiomas had meningothelial or microcystic architecture and were CNS WHO grade 1 (19 of 29 tumors), but