Optic nerve sheath meningiomas harbor distinct genetic variants

Area of Science:

• Neuro-oncology
• Molecular genetics
• Ophthalmology

Background:

• Optic nerve sheath meningiomas (pONSMs and sONSMs) present significant clinical challenges due to treatment-related visual loss.
• Standard treatments like surgery and radiation risk further optic nerve damage.
• The molecular pathology of pONSMs and sONSMs is not well understood compared to other meningiomas.

Purpose of the Study:

• To investigate the molecular genetic landscape of primary and secondary optic nerve sheath meningiomas using high-throughput techniques.
• To identify distinct genetic alterations in pONSMs and sONSMs that could be targeted for therapy.
• To explore potential avenues for vision preservation or improvement in patients with these tumors.

Main Methods:

• Next-generation sequencing was performed on 18 optic nerve sheath meningiomas (11 pONSMs, 7 sONSMs).
• Tumor samples were sourced from three distinct institutions.
• Comparative molecular analysis was conducted between pONSMs and sONSMs.

Main Results:

• Both pONSMs and sONSMs exhibited known gene variants found in other meningiomas.
• Distinct genetic alterations were identified in genes related to cell signaling, transcriptional regulation, and DNA damage repair.
• These findings highlight potential molecular differences between primary and secondary optic nerve sheath meningiomas.

Conclusions:

• The study provides novel insights into the molecular genetics of optic nerve sheath meningiomas.
• Identified genetic alterations expand the understanding of these understudied tumors.
• Findings may pave the way for developing targeted therapies to address unique therapeutic challenges and preserve vision.