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

Chaluts, Danielle; Dullea, Jonathan T; Ali, Muhammad; Vasan, Vikram; Devarajan, Alex; Rutland, John W; Gill, Corey M.; Ellis, Ethan; Kinoshita, Yayoi; McBride, Russell; Bederson, Joshua B.; Donovan, Michael; Sebra, Robert; Umphlett, Melissa; Shrivastava, Raj

doi:10.1007/s00432-022-04442-y

Cited by 6 publications

(6 citation statements)

References 31 publications

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“…With regards to meningiomas, a recent study identified CREBBP as present in aggressive meningiomas [ 11 ]. In previously reported results from this cohort, alterations in ARID1A, another chromatin-remodeling-related gene, were associated with an increased hazard of death and recurrence of primary tumors [ 8 , 9 ]. The present finding, in the context of the prior work, indicates that there may be a relationship between chromatin remodeling dysfunction and meningioma outcomes.…”

Section: Discussionmentioning

confidence: 96%

“…For mutations of interest, the specific alterations were visualized with the R package “mutsneedle” [ 27 ]. This cohort, and the associated sequencing data, have been previously reported [ 8 , 9 , 28 – 32 ].…”

Section: Methodsmentioning

confidence: 99%

“…Presently, the literature has comparatively few reports on the long-term outcomes of meningiomas stratified by genomic alteration. A recent set of studies utilizing the present dataset found that mutation in ARID1A was associated with increased hazard of death and recurrence of primary tumors [ 8 , 9 ]. Another study also related alterations in DREAM complex transcription with changes in the rate of meningioma recurrence [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Association between tumor mutations and meningioma recurrence in Grade I/II disease

et al. 2022

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Background: Meningiomas are common intracranial tumors with variable prognoses not entirely captured by commonly used classification schemes. We sought to determine the relationship between meningioma mutations and oncologic outcomes using a targeted next-generation sequencing panel. Materials and Methods: We identified 184 grade I and II meningiomas with both >90 days of post-surgical follow-up and linked targeted next-generation sequencing. For mutated genes in greater than 5% of the sample, we computed progression-free survival Cox-regression models stratified by gene. We then built a multi-gene model by including all gene predictors with a p -value of less than 0.20. Starting with that model, we performed backward selection to identify the most predictive factors. Results: ATM (HR = 4.448; 95% CI: 1.517–13.046), CREBBP (HR = 2.727; 95% CI = 1.163–6.396), and POLE (HR = 0.544; HR = 0.311–0.952) were significantly associated with alterations in disease progression after adjusting for clinical and pathologic factors. In the multi-gene model, only POLE remained a significant predictor of recurrence after adjusting for the same clinical covariates. Backwards selection identified recurrence status, resection extent, and mutations in ATM (HR = 7.333; 95% CI = 2.318–23.195) and POLE (HR = 0.413; 95% CI = 0.229–0.743) as predictive of recurrence. Conclusions: Mutations in ATM and CREBBP were associated with accelerated meningioma recurrence, and mutations in POLE were protective of recurrence. Each mutation has potential implications for treatment. The effect of these mutations on oncologic outcomes and as potential targets for intervention warrants future study.

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Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association between tumor mutations and meningioma recurrence in Grade I/II disease

et al. 2022

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“…A recent report among 71,301 patients suggests that liquid biopsies identified ARID1A alterations at a frequency similar to that found in primary tumor material [ 24 ]. If mutations in ARID1A are present in the primary tumor such as atypical meningiomas, these tumors tend to have a worse prognosis [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical and mutational profile of AT-rich interaction domain 1A-mutated cancers

Falcone,

Filetti,

Lombardi

et al. 2023

Exploration of Targeted Anti-Tumor Therapy

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Aim: AT-rich interaction domain 1A (ARID1A) encodes a key component of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex that participates in gene expression. ARID1A alterations are quite common among cancer patients, although their role remains debated. The aim of this article was to study ARID1A-mutated cancer patients. Methods: Molecular and clinical data of cancer patients evaluated at Phase 1 Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS were collected. Molecular analyses were performed using FoundationOne® CDx (Foundation Medicine Inc., Cambridge, MA, United States). Cancer patients with at least one molecular alteration in ARID1A gene were identified as ARID1A+. Results: Among the 270 patients undergoing molecular analysis, we found 25 (9%) with at least one pathogenic alteration in ARID1A. The vast majority of these patients were female (84%). The median age at diagnosis was 59; most of the cancers (15, 60%) were gynecological (especially endometrioid endometrial cancers and clear cell ovarian cancers), diagnosed at an early stage. Frameshift alterations in ARID1A were the most common (19/31, 61%) alterations. The median number of mutations in ARID1A+ population was higher compared to ARID1A– population (6 vs. 4), as well as tumor mutational burden (TMB) [20 mutations/megabase (mut/Mb) vs. 1.26 mut/Mb]. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphatase and tensin homolog (PTEN), catenin beta 1 (CTNNB1), and lysine methyltransferase 2D (MLL2) mutations were enriched in ARID1A+ population. In this cohort, ARID1A did not display any relation with response to platinum chemotherapy. Cancers with double alterations in ARID1A (ARID1A2+) were all gynecological cancers (83% endometrioid endometrial cancers). Conclusions: This analysis provides clinical and molecular details about the phenotypes of ARID1A+ cancers, in particular the subgroup of gynecologic cancers. The high frequency of concurrent mutations in the phosphoinositide 3-kinase (PI3K) pathway among endometrioid endometrial cancers may support the proposal of a new treatment strategy based on the combination of ataxia telangiectasia and Rad3-related (ATR) inhibitor and PIK3CA inhibitor.

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“…However, the research also highlighted that further prospective studies would be needed to validate ARID1A as a prognostic marker. This indicates that while the initial results are promising, more research is required to confirm ARID1A's utility as a biomarker (Chaluts, 2022). NF2 and SWI/SNF-Related, matrix-associated, actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1) are tumor suppressor genes that have been implicated in the development of meningiomas.…”

Section: Multiple-gene Dna Methylation Of Meningioma Biomarkersmentioning

confidence: 99%

DNA methylation meningioma biomarkers: attributes and limitations

Gao

Zhang

et al. 2023

Front. Mol. Neurosci.

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Meningioma, one of the most common primary central nervous system tumors, are classified into three grades by the World Health Organization (WHO) based on histopathology. The gold-standard treatment, surgical resection, is hampered by issues such as incomplete resection in some cases and a high recurrence rate. Alongside genetic alterations, DNA methylation, plays a crucial role in progression of meningiomas in the occurrence and development of meningiomas. The epigenetic landscape of meningioma is instrumental in refining tumor classification, identifying robust molecular markers, determining prognosis, guiding treatment selection, and innovating new therapeutic strategies. Existing classifications lack comprehensive accuracy, and effective therapies are limited. Methylated DNA markers, exhibiting differential characteristics across varying meningioma grades, serve as invaluable diagnostic tools. Particularly, combinatorial methylated markers offer insights into meningioma pathogenesis, tissue origin, subtype classification, and clinical outcomes. This review integrates current research to highlight some of the most promising DNA and promoter methylation markers employed in meningioma diagnostics. Despite their promise, the development and application of DNA methylation biomarkers for meningioma diagnosis and treatment are still in their infancy, with only a handful of DNA methylation inhibitors currently clinically employed for meningioma treatment. Future studies are essential to validate these markers and ascertain their clinical utility. Combinatorial methylated DNA markers for meningiomas have broad implications for understanding tumor development and progression, signaling a paradigm shift in therapeutic strategies for meningiomas.

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

Cited by 6 publications

References 31 publications

Association between tumor mutations and meningioma recurrence in Grade I/II disease

Association between tumor mutations and meningioma recurrence in Grade I/II disease

Clinical and mutational profile of AT-rich interaction domain 1A-mutated cancers

DNA methylation meningioma biomarkers: attributes and limitations

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