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Identification of shared genomic aberrations between angiomatous and microcystic meningiomas.

ABSTRACT: Background:Angiomatous and microcytic meningiomas are classified as rare subtypes of grade I meningiomas by World Health Organization (WHO). They typically exhibit distinct histopathological features as indicated by their WHO titles; however, these angiomatous and microcystic features are often intermixed. Recently, angiomatous meningiomas were reported to show characteristic chromosomal polysomies unlike the other WHO grade I meningiomas. In the present study, we hypothesize that microcystic meningiomas share similar cytogenetic abnormalities with angiomatous meningioma. Methods:We performed copy number analysis using single nucleotide polymorphism (SNP) arrays for three angiomatous and eight microcystic meningiomas. Of these, three angiomatous and three microcystic meningiomas were also analyzed by whole exome sequencing and RNA sequencing. Results:We first analyzed three angiomatous and three microcystic meningiomas for which both frozen tissues and peripheral blood were accessible. Copy number analysis confirmed previously reported multiple polysomies in angiomatous meningiomas, which were entirely replicated in microcystic meningiomas when analyzed on different analytical platforms with five additional samples prepared from formalin-fixed paraffin-embedded tumors. Polysomy of chromosome 5 was found in all cases, along with chromosome 6, 12, 17, 18, and 20 in more than half of the cases including both angiomatous and microcystic meningiomas. Furthermore, next generation sequencing did not reveal any distinctive somatic point mutations or differences in gene expression characterizing either angiomatous or microcystic meningiomas, indicating a common genetic mechanism underlying tumorigenesis. Conclusions:Angiomatous and microcystic meningiomas have substantially similar genetic profiles represented by the characteristic patterns of multiple polysomies originating from chromosome 5 amplification.

SUBMITTER: Kuroi Y

PROVIDER: S-EPMC7212863 | biostudies-literature | 2019 May-Dec

REPOSITORIES: biostudies-literature

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Identification of shared genomic aberrations between angiomatous and microcystic meningiomas.

Kuroi Yasuhiro Y Akagawa Hiroyuki H Shibuya Makoto M Onda Hideaki H Maegawa Tatsuya T Kasuya Hidetoshi H

Neuro-oncology advances 20190501 1

<h4>Background</h4>Angiomatous and microcytic meningiomas are classified as rare subtypes of grade I meningiomas by World Health Organization (WHO). They typically exhibit distinct histopathological features as indicated by their WHO titles; however, these angiomatous and microcystic features are often intermixed. Recently, angiomatous meningiomas were reported to show characteristic chromosomal polysomies unlike the other WHO grade I meningiomas. In the present study, we hypothesize that microc ...[more]

PMID: 32642661

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Project description:Psychiatric disorders and common epilepsies are heritable disorders with a high comorbidity and overlapping symptoms. However, the causative mechanisms underlying this relationship are poorly understood. Here we aimed to identify overlapping genetic loci between epilepsy and psychiatric disorders to gain a better understanding of their comorbidity and shared clinical features. We analysed genome-wide association study data for all epilepsies (n = 44 889), genetic generalized epilepsy (n = 33 446), focal epilepsy (n = 39 348), schizophrenia (n = 77 096), bipolar disorder (n = 406 405), depression (n = 500 199), attention deficit hyperactivity disorder (n = 53 293) and autism spectrum disorder (n = 46 350). First, we applied the MiXeR tool to estimate the total number of causal variants influencing the disorders. Next, we used the conjunctional false discovery rate statistical framework to improve power to discover shared genomic loci. Additionally, we assessed the validity of the findings in independent cohorts, and functionally characterized the identified loci. The epilepsy phenotypes were considerably less polygenic (1.0 K to 3.4 K causal variants) than the psychiatric disorders (5.6 K to 13.9 K causal variants), with focal epilepsy being the least polygenic (1.0 K variants), and depression having the highest polygenicity (13.9 K variants). We observed cross-trait genetic enrichment between genetic generalized epilepsy and all psychiatric disorders and between all epilepsies and schizophrenia and depression. Using conjunctional false discovery rate analysis, we identified 40 distinct loci jointly associated with epilepsies and psychiatric disorders at conjunctional false discovery rate <0.05, four of which were associated with all epilepsies and 39 with genetic generalized epilepsy. Most epilepsy risk loci were shared with schizophrenia (n = 31). Among the identified loci, 32 were novel for genetic generalized epilepsy, and two were novel for all epilepsies. There was a mixture of concordant and discordant allelic effects in the shared loci. The sign concordance of the identified variants was highly consistent between the discovery and independent datasets for all disorders, supporting the validity of the findings. Gene-set analysis for the shared loci between schizophrenia and genetic generalized epilepsy implicated biological processes related to cell cycle regulation, protein phosphatase activity, and membrane and vesicle function; the gene-set analyses for the other loci were underpowered. The extensive genetic overlap with mixed effect directions between psychiatric disorders and common epilepsies demonstrates a complex genetic relationship between these disorders, in line with their bi-directional relationship, and indicates that overlapping genetic risk may contribute to shared pathophysiological and clinical features between epilepsy and psychiatric disorders.

Dataset Information

Identification of shared genomic aberrations between angiomatous and microcystic meningiomas.

Publications

Identification of shared genomic aberrations between angiomatous and microcystic meningiomas.

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