Genetic Profiling by Single‐Nucleotide Polymorphism‐Based Array Analysis Defines Three Distinct Subtypes of Orbital Meningioma

Ho, Cheng Ying; Mosier, Stacy; Safneck, Janice R.; Salomão, Diva R.; Miller, Neil R.; Eberhart, Charles G.; Gocke, Christopher D.; Batista, Denise; Rodríguez, Fausto J.

doi:10.1111/bpa.12150

Cited by 21 publications

(10 citation statements)

References 45 publications

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“…A notable study showed chromosome 22q loss in 10/14 patients with orbital meningioma but only 1/5 with optic nerve sheath meningioma. 27 Another molecular change included copy number alterations involving chromosome 2. 27 There have been no prior reports of a gene mutation in TRAF7 in a primary optic nerve sheath meningioma specimen.…”

Section: Discussionmentioning

confidence: 99%

TRAF7 somatic mosaicism in a patient with bilateral optic nerve sheath meningiomas: illustrative case

Kaidonis¹,

Pekmezci²,

Ziffle³

et al. 2022

Journal of Neurosurgery: Case Lessons

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BACKGROUND In the past decade, next-generation sequencing has spurred significant progress in the understanding of cytogenetic alterations that occur in meningiomas. Eighty percent of adult meningiomas harbor pathogenic somatic variants involving NF2, TRAF7, SMARCB1, KLF4, PI3K, or POLR2A. Somatic variants in TRAF7 associated with meningiomas usually localize to the gene’s WD40 domains but are mutually exclusive to germline mutations, which cause a distinctive autosomal dominant syndrome. OBSERVATIONS This case involved a 15-year-old girl with bilateral optic nerve sheath meningiomas, diffuse meningiomatosis, and syndromic features, including craniosynostosis, brain anomalies, syndactyly, brachydactyly, epicanthus, and patent ductus arteriosus. Genetic testing of the meningioma specimen 7 years after biopsy showed a pathogenic p.R641C variant within the WD40 domain of the TRAF7 gene. Additional testing of unaffected tissues identified the same variant at lower allele frequencies, consistent with postzygotic somatic mosaicism. LESSONS The authors report postzygotic somatic mosaicism for a p.R641C variant in the TRAF7 gene in a patient with bilateral optic nerve sheath meningiomas, diffuse meningiomatosis and a constellation of systemic findings previously recognized in patients with germline mutations of this gene. This is the first report of optic nerve sheath meningioma in a patient with mutation in the TRAF7 gene.

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Section: Discussionmentioning

confidence: 99%

TRAF7 somatic mosaicism in a patient with bilateral optic nerve sheath meningiomas: illustrative case

Kaidonis¹,

Pekmezci²,

Ziffle³

et al. 2022

Journal of Neurosurgery: Case Lessons

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“…Conventional cytogenetic analysis was performed using standard karyotyping methods in two cases and single‐nucleotide polymorphism (SNP) arrays in five cases, using previously published approaches . In brief, for the SNP array pinpoint reagents (ZymoResearch, Orange, CA, USA) were used to isolate tumor regions.…”

Section: Methodsmentioning

confidence: 99%

Granular cell astrocytoma: an aggressive IDH‐wildtype diffuse glioma with molecular genetic features of primary glioblastoma

et al. 2018

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Granular cell astrocytoma (GCA) is a rare adult infiltrating glioma subtype. We studied a series of 39 GCAs. Median age of presentation was 57.8 years and most cases developed in the frontal or temporal lobes. Tumors included grade II (n = 14), grade III (n = 11), and grade IV (n = 14) by WHO criteria. Granular cell morphology was diffuse in 31 (79%) cases and partial in eight (21%). Immunohistochemistry showed frequent positivity for GFAP (28 of 31), OLIG2 (16 of 16), and CD68 (27 of 30), but HAM56, CD163, and IBA-1 histiocytic markers were all negative (22 of 22). IDH1(R132H) was negative in all the cases tested (16 of 16), while ATRX expression was retained (12 of 12). Cytogenetics demonstrated monosomy 10 (6 of 6) cases, +7 in 4 (of 6), -13q in 4 of 6, and -14 in 4 of 6. Next-generation sequencing demonstrated mutations in PTEN/PIK3 genes in 6/13 (46%), NF1 in 3 of 10 (30%), TP53 in 3 of 13 (23%), PALB2 in 3 of 10 (30%), STAG2 in 3 of 10 (30%), EGFR mutation/amplification in 3 of 13 (23%), and AR in 2 of 10 (20%). CDKN2A/B deletion was identified in 5 of 13 (30%) cases (homozygous deletion in 4). The TERT C228T mutation was identified in 9 of 13 (69%). No mutations were encountered in IDH1, IDH2, CIC, FUBP1, H3F3A, BRAF or ATRX genes. The mean overall survival was 11.3 months. Patients >60 years old at diagnosis had a worse survival than patients <60 years (P = 0.001). There were no statistically significant differences in survival by WHO grade, extent of granular cell change, sex or MIB-1 (P > 0.05). GCA is a variant of IDH-wildtype diffuse glioma with aggressive behavior irrespective of grade and extent of granular cell morphology, and with molecular genetic features corresponding to primary glioblastoma.

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“…Several studies have also revealed that chromosomal aberrations, such as 1p/14q codeletion, correlate with recurrence ( 30 – 33 ). In one study of mostly grade I orbital meningiomas, progressive tumors were more likely to have loss of chromosome 1p and 6q ( 34 ). Specific metabolite concentrations within tumor tissue have also been associated with clinical outcome.…”

Section: Molecular Drivers Of Meningioma Recurrence and Progressionmentioning

confidence: 99%

Synthesizing Molecular and Immune Characteristics to Move Beyond WHO Grade in Meningiomas: A Focused Review

et al. 2022

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No portion of this manuscript has previously been presented. Meningiomas, the most common primary intracranial tumors, are histologically categorized by the World Health Organization (WHO) grading system. While higher WHO grade is generally associated with poor clinical outcomes, a significant subset of grade I tumors recur or progress, indicating a need for more reliable models of meningioma behavior. Several groups have developed risk scores based on molecular or immunologic characteristics. These classification schemes show promise, with several models preliminarily demonstrating similar or superior accuracy to WHO grading. Improved understanding of immune system recognition and targeting of meningioma subtypes is necessary to advance the predictive power, as well as develop new therapies. Here, we characterize meningioma molecular drivers, predictive of recurrence and progression, and describe specific aspects of the immune response to meningiomas while highlighting critical questions and ongoing research. Relevant manuscripts of interest were identified using a systematic approach and synthesized into this focused review. Finally, we summarize the ongoing and completed clinical trials for immunotherapy in meningiomas and offer perspective on future directions.

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Genetic Profiling by Single‐Nucleotide Polymorphism‐Based Array Analysis Defines Three Distinct Subtypes of Orbital Meningioma

Cited by 21 publications

References 45 publications

TRAF7 somatic mosaicism in a patient with bilateral optic nerve sheath meningiomas: illustrative case

TRAF7 somatic mosaicism in a patient with bilateral optic nerve sheath meningiomas: illustrative case

Granular cell astrocytoma: an aggressive IDH‐wildtype diffuse glioma with molecular genetic features of primary glioblastoma

Synthesizing Molecular and Immune Characteristics to Move Beyond WHO Grade in Meningiomas: A Focused Review

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