Genetic Alterations in Skull Base Meningiomas
| Autor: | Ossama Al-Mefty, Malak Abedalthagafi, Yu Mei, Azra H. Ligon, Wenya Linda Bi, Ian F. Dunn, Rameen Beroukhim, Brian M. Alexander, Sandro Santagata |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Journal of Neurological Surgery Part B: Skull Base. 76 |
| ISSN: | 2193-634X 2193-6331 |
| Popis: | Background: The genetic underpinning of meningiomas remains incompletely understood, despite their prevalence in adults. We prospectively analyzed the genetic profiles of a large cohort of skull base meningiomas and assessed relevant pathological and clinical variables. Methods: Copy-number alterations were analyzed on resected skull base meningiomas using array-based comparative genomic hybridization. Pathologic features and clinical factors associated with outcome were also assessed. Results: A total of 83 skull base meningiomas from 80 patients (49F/31M; mean age, 55 years; range, 22–90 years) were profiled following surgical resection. The majority of tumors were de novo, undergoing primary resection, 27 tumors were recurrent, and 7 patients harbored multiple intracranial meningiomas. Overall, 19 tumors had prior radiation exposure, 3 being radiation induced, and 15 patients received postoperative adjuvant radiation. The most common tumor locations were petroclival/petrosal (26), sphenoid wing (13), parasagittal/falcine (12), planum sphenoidale/olfactory groove (9), and tuberculum/clinoid (8), followed by intraventricular, middle fossa, tentorial, torcular, cavernous sinus, and foramen magnum locations. Among the tumors, 59 were WHO grade I (28 meningothelial, 11 fibroblastic, 10 transitional, 4 secretory, 4 angiomatous, and 2 psammomatous); 18 were grade II (17 atypical and 1 clear cell); and 6 were grade III (five anaplastic and one rhabdoid). Overall, 8 tumors were observed to exhibit brain invasion and 19 cases had intratumoral necrosis. Across all tumors, monosomy 22 was the most frequent copy number alteration, occurring in 47% of all samples (29% of grade I tumors, 89% of grade II tumors, and 100% of grade III meningiomas). The following alterations were frequently observed, particularly in anaplastic tumors: loss of chromosome 1p (all: 30%, grade I: 10%, grade II: 78%, and grade III: 83%); 6q (all: 22%, grade I: 5%, grade II: 50%, and grade III: 100%); 7p (all: 13%, grade I: 0%, grade II: 33%, and grade III: 83%); 10q (all: 8%, grade I: 2%, grade II: 22%, and grade III: 33%); and 18q (all: 16%, grade I: 3%, grade II: 33%, and grade III: 83%). The incidence of chromosomal loss varied significantly by location. Paravenous meningiomas, involving the sagittal sinus, torcula, and cavernous sinus, harbored an especially high rate of chromosomal loss (1p-: 65%; 6q-: 29%; 18q-: 29%; and monosomy 22: 76%). Petrosal/petroclival (1p-: 32%; 6q-: 23%; 18q-: 14%; and monosomy 22: 59%) and sphenoid (1p-: 23%; 6q-: 15%; 18q-: 8%; and monosomy 22: 31%) meningiomas also expressed higher chromosomal losses than planum sphenoidale/olfactory (1p-: 0%; 6q-: 0%; 18q-: 11%; and monosomy 22: 0%) and tuberculum/clinoid (1p-: 0%; 6q-: 0%; 18q-: 0%; and monosomy 22: 0%) meningiomas, which featured fewer copy number alterations. Polysomy involving multiple chromosomes was a marked feature of angiomatous meningiomas. Furthermore, patterns of intratumoral heterogeneity emerged from an illustrative case. Conclusion: Traditional histopathologic classifications fail to fully account for the natural history and growth patterns of intracranial meningiomas. Systematic genomic characterization of a large series of skull base meningiomas reveals distinct subsets of tumors, which may be further correlated with clinical outcomes. |
| Databáze: | OpenAIRE |
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