Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
J Cancer Res Clin Oncol. 2021 Nov;147(11):3431-3440. doi: 10.1007/s00432-021-03586-7. Epub 2021 Mar 14.
While SWI/SNF chromatin remodeling complex alterations occur in approximately 20% of cancer, the frequency and potential impact on clinical outcomes in meningiomas remains to be comprehensively elucidated.
A large series of 255 meningiomas from a single institution that was enriched for high grade and recurrent lesions was identified. We performed next-generation targeted sequencing of known meningioma driver genes, including NF2, AKT1, PIK3CA, PIK3R1, and SMO and SWI/SNF chromatin remodeling complex genes, including ARID1A, SMARCA4, and SMARCB1 in all samples. Clinical correlates focused on clinical presentation and patient outcomes are presented.
The series included 63 grade I meningiomas and 192 high-grade meningiomas, including 173 WHO grade II and 19 WHO grade III. Samples from recurrent surgeries comprised 37.3% of the series. A total of 41.6% meningiomas were from the skull base. NF2, AKT1, PIK3CA, PIK3R1, and SMO were mutated in 40.8, 7.1, 3.5, 3.9, and 2.4% of samples, respectively. ARID1A, SMARCA4, and SMARCB1 mutations were observed in 17.3, 3.5, and 5.1% of samples, respectively. A total of 68.2% of ARID1A-mutant meningiomas harbored a p.Gln1327del in-frame deletion. ARID1A mutations were seen in 19.1% of Grade I, 16.8% of Grade II, and 15.8% of Grade III meningiomas (P = 0.9, Fisher's exact). Median overall survival was 16.3 years (95% CI 10.9, 16.8). With multivariable analysis, the presence of an ARID1A mutation was significantly associated with a 7.421-fold increased hazard of death (P = 0.04).
ARID1A mutations occur with similar frequency between low and high-grade meningiomas, but ARID1A mutations are independently prognostic of worse prognosis beyond clinical and histopathologic features.
虽然 SWI/SNF 染色质重塑复合物改变发生在大约 20%的癌症中，但脑膜瘤中的频率和对临床结果的潜在影响仍有待全面阐明。
从一个机构中确定了一个大型的 255 例脑膜瘤系列，这些脑膜瘤富含高级别和复发性病变。我们对已知的脑膜瘤驱动基因，包括 NF2、AKT1、PIK3CA、PIK3R1 和 SMO 以及 SWI/SNF 染色质重塑复合物基因，包括 ARID1A、SMARCA4 和 SMARCB1，进行了下一代靶向测序。介绍了侧重于临床表现和患者结局的临床相关性。
该系列包括 63 例 I 级脑膜瘤和 192 例高级别脑膜瘤，包括 173 例 WHO 2 级和 19 例 WHO 3 级。复发性手术样本占系列的 37.3%。共有 41.6%的脑膜瘤来自颅底。NF2、AKT1、PIK3CA、PIK3R1 和 SMO 的突变分别发生在 40.8%、7.1%、3.5%、3.9%和 2.4%的样本中。ARID1A、SMARCA4 和 SMARCB1 突变分别发生在 17.3%、3.5%和 5.1%的样本中。总共有 68.2%的 ARID1A 突变脑膜瘤携带框内缺失的 p.Gln1327del。ARID1A 突变见于 19.1%的 I 级、16.8%的 II 级和 15.8%的 III 级脑膜瘤（P=0.9，Fisher 确切检验）。中位总生存期为 16.3 年（95%CI 10.9,16.8）。多变量分析显示，ARID1A 突变与死亡风险增加 7.421 倍显著相关（P=0.04）。
ARID1A 突变在低级别和高级别脑膜瘤之间发生的频率相似，但 ARID1A 突变是独立于临床和组织病理学特征的预后不良的预测因素。
