家族性和散发性脑膜瘤基因中的新型种系和体细胞变异。

Novel germline and somatic variants in familial and sporadic meningioma genes.

作者信息

Bencheikh Bouchra Ouled Amar, Dilliott Allison A, Gauthier Julie, Laurent Sandra Beatrice, Ambalavanan Amirthagowri, Spiegelman Dan, Dionne-Laporte Alexandre, Lyahyai Jaber, Martuza Robert L, Sieb Jörn P, Farhan Sali M K, Dion Patrick A, Pulst Stefan-M, Rouleau Guy A

机构信息

Montreal Neurological Institute, McGill University, Montréal, QC, Canada.

Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada.

出版信息

NPJ Genom Med. 2025 May 15;10(1):41. doi: 10.1038/s41525-025-00494-4.

DOI:10.1038/s41525-025-00494-4

PMID:40374631

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12081709/

Abstract

Meningiomas arise from arachnoid cells in the meninges surrounding the brain and spinal cord and are attributed to NF2 pathogenic variants in, approximately 60% of cases. Using exome sequencing, we found heterozygous germline variants in nine potential novel meningioma genes across four families and four sporadic cases. We then screened for germline and somatic variants in these genes and 11 known meningioma genes in 76 sporadic meningiomas blood/tumor pairs. We identified 18 germline and 58 somatic variants in 18 of the 20 genes, including seven of our newly proposed meningioma genes: CSMD3, EXTL3, FAT3, RAB44, RARA, RECQL4, and TNRC6A. Chromosomal abnormalities were identified in 39 of 49 tumors that also carried germline or somatic variants, with 71.8% encompassing NF2. This study provides potential novel genetic risk factors of meningiomas appropriate for further exploration from the greater scientific community and pathways to consider in the design of future therapeutic approaches.

摘要

脑膜瘤起源于脑和脊髓周围脑膜中的蛛网膜细胞，约60%的病例归因于NF2致病变异。通过外显子组测序，我们在四个家族和四个散发性病例中的九个潜在新型脑膜瘤基因中发现了杂合种系变异。然后，我们在76对散发性脑膜瘤的血液/肿瘤样本中筛选了这些基因以及11个已知脑膜瘤基因中的种系和体细胞变异。我们在20个基因中的18个基因中鉴定出18个种系变异和58个体细胞变异，包括我们新提出的七个脑膜瘤基因：CSMD3、EXTL3、FAT3、RAB44、RARA、RECQL4和TNRC6A。在49个同时携带种系或体细胞变异的肿瘤中，有39个发现了染色体异常，其中71.8%涉及NF2。本研究提供了脑膜瘤潜在的新型遗传风险因素，适合广大科学界进一步探索，以及未来治疗方法设计中需要考虑的途径。