Genetic Profiling of Orbital and Optic Nerve Meningiomas by Single-Nucleotide Polymorphism-Based Array Analysis
Cheng-Ying Ho, Stacy Mosier, Charles Eberhart, Christopher D Gocke, Denise AS Batista, Fausto J Rodriguez. The Johns Hopkins Hospital, Baltimore, MD
Background: Meningiomas account for approximately 4% of all intraorbital tumors. Based on the location, intraorbital meningiomas can be subclassified as primary lesions thought to be derived from the intraorbital lining (Ob) or, less commonly, intracanalicular segments of the optic nerve (ON). To date, the cytogenetic features of intraorbital meningiomas have not been delineated. With the development of single-nucleotide polymorphism (SNP) arrays, a high-resolution screening method for genetic alterations in these tumors is now available.
Design: Six cases of intraorbital meningiomas including 5 cases of Ob and one case of ON meningioma were retrieved from our surgical pathology archives from 2008 to 2011. All cases included in the study were grade I based on the WHO classification. DNA was extracted from formalin-fixed, paraffin-embedded tissue (FFPE) and hybridized on the 300k Illumina SNP array.
Results: SNP array analysis showed genetic alterations in 5 of 6 (83%) intraorbital meningiomas, including 4 Ob and one ON meningioma. Four of six (67%) cases had multiple (> 1) genetic alterations. Four of five (80%) Ob meningiomas exhibited either monosomy 22 or loss of 22q. The second most frequent alteration in Ob meningiomas was deletion of 6q (3 of 5 cases; 60%), which appears to be associated with a high proliferation rate, high-grade morphology and recurrence in cranial meningiomas. Other less common alterations detected in Ob meningiomas included partial loss of 1p, monosomy 4, loss of 7p and loss of 19p. Interestingly, the only case of ON meningioma demonstrated a unique genotype with deletion of 1pter-p35.3, deletion of 2pter-p16.3, deletion 2q22.1-qter and gain of 15q21.3-qter. The latter chromosomal aberrations are uncommon in cranial menigiomas. Additional cases are being studied to address whether ON meningiomas have a genetic composition distinct from that of Ob and cranial meningiomas.
Conclusions: Intraorbital meningiomas appear to show frequent chromosomal alterations even in grade I tumors. Compared to cranial meningiomas, Ob meningiomas display more frequent loss of 6q, which is known to be associated with progression and poor prognosis. Our study also suggests that ON meningioma could potentially be a unique clinicopathologic and molecular entity.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 268, Tuesday Afternoon