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ARID1A 突变与非典型脑膜瘤的复发和较短的无进展生存期相关。

ARID1A mutation associated with recurrence and shorter progression-free survival in atypical meningiomas.

机构信息

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue; Floor 8, New York, NY, 10129, USA.

Sema4, A Mount Sinai Venture, Stamford, CT, USA.

出版信息

J Cancer Res Clin Oncol. 2023 Jul;149(8):5165-5172. doi: 10.1007/s00432-022-04442-y. Epub 2022 Nov 9.

Abstract

PURPOSE

The oncologic outcomes for atypical meningiomas can be poor. Generally, patients that have had a prior recurrence have a substantially elevated risk of a future recurrence. Additionally, certain tumor genomic profiles have been shown as markers of poor prognosis. We sought to characterize the genomic differences between primary and recurrent tumors as well as assess if those differences had implications on recurrence.

METHODS

We identified primary and recurrent gross totally resected WHO grade II meningiomas with > 30 days of post-surgical follow-up at our institution. For genes with a prevalence of > 5% in the cohort, we compared the mutational prevalence in primary and recurrent tumors. For a gene of interest, we assessed the time to radiographic recurrence using adjusted cox-regression.

RESULTS

We identified 88 meningiomas (77 primary, 16 recurrent) with a median follow-up of 5.33 years. Mutations in ARID1A found in association with recurrent tumors (7/16 recurrent tumors vs 5/72 primary tumors, p < 0.001). In the whole cohort, mutations in ARID1A were not associated with alterations in time to recurrence after adjusting for recurrence status (p = 0.713). When restricted to primary tumors, ARID1A is associated with a 625% increase in the hazard of recurrence (HR = 7.26 [1.42-37.0]; p = 0.017).

CONCLUSION

We demonstrate mutations in ARID1A, a chromatin remodeling gene, in a higher prevalence in recurrent tumors. We further demonstrate that when mutations in ARID1A are present in primary atypical meningiomas, these tumors tend to have worse prognosis. Further prospective study may validate ARID1A as a prognostic marker.

摘要

目的

非典型脑膜瘤的肿瘤学结果可能较差。一般来说,曾经复发过的患者未来复发的风险会大大增加。此外,某些肿瘤基因组特征已被证明是预后不良的标志物。我们试图描述原发性和复发性肿瘤之间的基因组差异,并评估这些差异是否对复发有影响。

方法

我们在本机构确定了原发性和复发性完全切除的 WHO 二级脑膜瘤,这些肿瘤在手术后有超过 30 天的随访期。对于在队列中患病率超过 5%的基因,我们比较了原发性和复发性肿瘤中的突变患病率。对于一个感兴趣的基因,我们使用调整后的 cox 回归评估了放射影像学复发的时间。

结果

我们确定了 88 例脑膜瘤(77 例原发性,16 例复发性),中位随访时间为 5.33 年。在复发性肿瘤中发现 ARID1A 突变与复发性肿瘤有关(7/16 例复发性肿瘤与 5/72 例原发性肿瘤相比,p<0.001)。在整个队列中,在调整了复发状态后,ARID1A 突变与复发时间的改变无关(p=0.713)。当仅限于原发性肿瘤时,ARID1A 与复发的风险增加 625%相关(HR=7.26[1.42-37.0];p=0.017)。

结论

我们证明了染色质重塑基因 ARID1A 中的突变在复发性肿瘤中更为常见。我们进一步证明,当 ARID1A 中的突变存在于原发性非典型脑膜瘤中时,这些肿瘤往往预后较差。进一步的前瞻性研究可能会验证 ARID1A 作为预后标志物的价值。

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