Suppr超能文献

对一名患者中具有不同组织病理学表现的多个脑膜瘤进行全外显子组测序,结果显示出独特的体细胞突变负担和独立的克隆起源。

Whole exome sequencing of multiple meningiomas with varying histopathological presentation in one patient revealed distinctive somatic mutation burden and independent clonal origins.

作者信息

Sheng Han-Song, Shen Fang, Zhang Nu, Yu Li-Sheng, Lu Xiang-Qi, Zhang Zhe, Fang Huang-Yi, Zhou Ling-Li, Lin Jian

机构信息

Department of Neurosurgery, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.

Department of Orthopedic Surgery's Spine Division, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, People's Republic of China.

出版信息

Cancer Manag Res. 2019 May 6;11:4085-4095. doi: 10.2147/CMAR.S202394. eCollection 2019.

Abstract

Although meningiomas are common intracranial tumors, multiple meningiomas (MMs) are rare entities in patients without neurofibromatosis type 2. Previous studies suggest most sporadic MMs are of monoclone in origin. To elucidate the clonal relationship between two sporadic meningiomas from the same patient by using the next-generation sequencing (NGS) platform. Two MMs, located frontally and parietally on the right side, were surgically removed from a 52-year-old male. Pathological examinations and whole exome sequencing were performed on tumor samples, followed by Sanger sequencing validation. MMs were diagnosed as secretory and fibrous subtypes, respectively, on histology (WHO grade I) and tumor DNA exhibited distinctive somatic mutation patterns. Specifically, the secretory subtype carried more single nucleotide variant while the fibrous subtype had much higher copy number variation. Besides, the two tumors demonstrated different mutation profiles in predisposing genes and known driver mutations. For example, the secretory subtype had missense mutations in and , while the fibrous subtype had frameshift deletion of gene in addition to copy number loss of and , genetic events that have already been associated with the development of meningiomas. Significantly mutated gene analysis revealed novel mutations of in the secretory subtype and and in the fibrous subtype. Sanger sequencing validated important point mutations in (c.1678G>A, .G560S), (c.1225A>C, .K409Q) and (c.169T>G, .W57G). Our data suggest the two meningiomas might develop independently in this patient and molecular subtyping by NGS is a valuable supplement to conventional pathology. Further study is needed to ascertain whether these novel genetic events are tumorigenic or simply passenger mutations, as well as their clinical implications.

摘要

虽然脑膜瘤是常见的颅内肿瘤,但在无2型神经纤维瘤病的患者中,多发性脑膜瘤(MMs)是罕见的。先前的研究表明,大多数散发性MMs起源于单克隆。通过使用下一代测序(NGS)平台来阐明同一患者的两个散发性脑膜瘤之间的克隆关系。从一名52岁男性患者身上手术切除了位于右侧额叶和顶叶的两个MMs。对肿瘤样本进行了病理检查和全外显子测序,随后进行了桑格测序验证。组织学上(WHO I级),MMs分别被诊断为分泌型和纤维型亚型,肿瘤DNA表现出独特的体细胞突变模式。具体而言,分泌型亚型携带更多的单核苷酸变异,而纤维型亚型具有更高的拷贝数变异。此外,这两个肿瘤在易感基因和已知驱动突变方面表现出不同的突变谱。例如,分泌型亚型在[基因名称1]和[基因名称2]中有错义突变,而纤维型亚型除了[基因名称3]和[基因名称4]的拷贝数缺失外,还有[基因名称5]的移码缺失,这些基因事件已经与脑膜瘤的发生相关。显著突变基因分析揭示了分泌型亚型中[基因名称6]的新突变以及纤维型亚型中[基因名称7]和[基因名称8]的新突变。桑格测序验证了[基因名称6](c.1678G>A,p.G560S)、[基因名称7](c.1225A>C,p.K409Q)和[基因名称8](c.169T>G,p.W57G)中的重要点突变。我们的数据表明,这两个脑膜瘤可能在该患者中独立发生,并且通过NGS进行分子亚型分类是对传统病理学的有价值补充。需要进一步研究以确定这些新的基因事件是致瘤性的还是仅仅是过客突变,以及它们的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d862/6510395/e4408805cf07/CMAR-11-4085-g0001.jpg

相似文献

2
Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations.
Acta Neuropathol. 2013 Mar;125(3):351-8. doi: 10.1007/s00401-013-1093-x. Epub 2013 Feb 12.
7
Comprehensive genomic analysis reveals clonal origin and subtype-specific evolution in a case of sporadic multiple meningiomas.
Brain Tumor Pathol. 2024 Oct;41(3-4):132-138. doi: 10.1007/s10014-024-00486-9. Epub 2024 Jul 27.
8
Specific gene expression signatures of low grade meningiomas.
Front Oncol. 2023 Mar 1;13:1126550. doi: 10.3389/fonc.2023.1126550. eCollection 2023.
9
Non-NF2 mutations have a key effect on inhibitory immune checkpoints and tumor pathogenesis in skull base meningiomas.
J Neurooncol. 2019 Aug;144(1):11-20. doi: 10.1007/s11060-019-03198-9. Epub 2019 Jun 8.

引用本文的文献

1
Multiple meningiomas of different variants in a single patient: illustrative cases.
J Neurosurg Case Lessons. 2025 Mar 3;9(9). doi: 10.3171/CASE24359.
2
Comprehensive genomic analysis reveals clonal origin and subtype-specific evolution in a case of sporadic multiple meningiomas.
Brain Tumor Pathol. 2024 Oct;41(3-4):132-138. doi: 10.1007/s10014-024-00486-9. Epub 2024 Jul 27.
3
A rare case report of infratentorial cisternal angiolipoma with review of literature.
Childs Nerv Syst. 2024 Feb;40(2):549-553. doi: 10.1007/s00381-023-06099-5. Epub 2023 Aug 8.
4
Multiple meningiomas: Epidemiology, management, and outcomes.
Neurooncol Adv. 2023 Jun 3;5(Suppl 1):i35-i48. doi: 10.1093/noajnl/vdac108. eCollection 2023 May.
7
Genomic profiling of sporadic multiple meningiomas.
BMC Med Genomics. 2022 May 14;15(1):112. doi: 10.1186/s12920-022-01258-0.
9
Sporadic multiple meningiomas harbor distinct driver mutations.
Acta Neuropathol Commun. 2021 Jan 6;9(1):8. doi: 10.1186/s40478-020-01113-2.

本文引用的文献

1
Familial Syndromes Involving Meningiomas Provide Mechanistic Insight Into Sporadic Disease.
Neurosurgery. 2018 Dec 1;83(6):1107-1118. doi: 10.1093/neuros/nyy121.
2
Hereditary SWI/SNF complex deficiency syndromes.
Semin Diagn Pathol. 2018 May;35(3):193-198. doi: 10.1053/j.semdp.2018.01.002. Epub 2018 Feb 1.
3
Meningiomas with different histological grade in the same patient: Case report.
Medicine (Baltimore). 2017 Dec;96(50):e9086. doi: 10.1097/MD.0000000000009086.
5
Advances in meningioma genetics: novel therapeutic opportunities.
Nat Rev Neurol. 2018 Feb;14(2):106-115. doi: 10.1038/nrneurol.2017.168. Epub 2018 Jan 5.
6
Krüppel Like Factors Family Expression in Cervical Cancer Cells.
Arch Med Res. 2017 May;48(4):314-322. doi: 10.1016/j.arcmed.2017.06.011.
7
Management of multiple meningiomas.
J Neurosurg. 2018 May;128(5):1403-1409. doi: 10.3171/2017.2.JNS162608. Epub 2017 Jul 21.
8
Genetic and epigenetic alterations in meningiomas.
Clin Neurol Neurosurg. 2017 Jul;158:119-125. doi: 10.1016/j.clineuro.2017.05.002. Epub 2017 May 3.
9
DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis.
Lancet Oncol. 2017 May;18(5):682-694. doi: 10.1016/S1470-2045(17)30155-9. Epub 2017 Mar 15.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验