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血管母细胞瘤型和微囊型脑膜瘤之间共享基因组畸变的鉴定。

Identification of shared genomic aberrations between angiomatous and microcystic meningiomas.

作者信息

Kuroi Yasuhiro, Akagawa Hiroyuki, Shibuya Makoto, Onda Hideaki, Maegawa Tatsuya, Kasuya Hidetoshi

机构信息

Department of Neurosurgery, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.

Tokyo Women's Medical University, Institute for Integrated Medical Sciences (TIIMS), Tokyo, Japan.

出版信息

Neurooncol Adv. 2019 Sep 28;1(1):vdz028. doi: 10.1093/noajnl/vdz028. eCollection 2019 May-Dec.

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.

摘要

背景

血管母细胞瘤型和微囊型脑膜瘤被世界卫生组织(WHO)归类为I级脑膜瘤的罕见亚型。它们通常表现出WHO命名所指示的独特组织病理学特征;然而,这些血管母细胞瘤样和微囊特征常常相互混杂。最近,有报道称血管母细胞瘤型脑膜瘤表现出与其他WHO I级脑膜瘤不同的特征性染色体多体性。在本研究中,我们假设微囊型脑膜瘤与血管母细胞瘤型脑膜瘤具有相似的细胞遗传学异常。

方法

我们使用单核苷酸多态性(SNP)阵列对3例血管母细胞瘤型和8例微囊型脑膜瘤进行了拷贝数分析。其中,3例血管母细胞瘤型和3例微囊型脑膜瘤还进行了全外显子测序和RNA测序。

结果

我们首先分析了3例血管母细胞瘤型和3例微囊型脑膜瘤,这些病例既有冷冻组织又有外周血。拷贝数分析证实了先前报道的血管母细胞瘤型脑膜瘤中的多个多体性,当在不同分析平台上对另外5个福尔马林固定石蜡包埋肿瘤制备的样本进行分析时,微囊型脑膜瘤中完全重现了这些多体性。在所有病例中均发现了5号染色体多体性,在包括血管母细胞瘤型和微囊型脑膜瘤在内的超过半数病例中还发现了6号、12号、17号、18号和20号染色体多体性。此外,二代测序未发现血管母细胞瘤型或微囊型脑膜瘤具有任何独特的体细胞点突变或基因表达差异,这表明肿瘤发生存在共同的遗传机制。

结论

血管母细胞瘤型和微囊型脑膜瘤具有基本相似的遗传谱,其特征是源于5号染色体扩增的多个多体性模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5690/7212863/6452a2e6b6ab/vdz028f0001.jpg

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