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

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

TLDR

  • A study identified potential novel genetic risk factors of meningiomas in 18 of 20 genes analyzed, including seven newly proposed genes.
  • The findings could improve our understanding of meningioma pathogenesis and inform the development of personalized treatment strategies.

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.

Overview

  • The study aims to identify genetic mutations associated with meningiomas, a type of tumor that arises from arachnoid cells in the meninges surrounding the brain and spinal cord.
  • The researchers used exome sequencing to analyze genetic variants in four families and four sporadic cases of meningioma, and then validated their findings in 76 sporadic meningioma blood/tumor pairs.
  • The primary objective of the study is to identify potential novel genetic risk factors of meningiomas and explore new therapeutic approaches.

Comparative Analysis & Findings

  • The study identified 18 germline and 58 somatic variants in 18 of the 20 genes analyzed, including seven 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.
  • The findings suggest that these genetic variants could be used to develop new diagnostic and therapeutic strategies for meningiomas.

Implications and Future Directions

  • The study's findings have the potential to improve our understanding of the genetic risk factors of meningiomas and inform the development of personalized treatment strategies.
  • Future studies should focus on validating the clinical significance of these genetic variants and exploring their role in the pathogenesis of meningiomas.
  • The study's novel genetic risk factors and pathways could also inform the design of future therapeutic approaches, such as targeted therapies or gene therapies.
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