Simple Summary
It has been known for several years that a loss of heterozygosity (LOH) on chromosome 1p, especially LOH on chromosome 1p36, is an independent marker of meningioma recurrence and progression. We aim to identify a factor that may be responsible for this effect. The ARID1A (AT-rich interactive domain-containing protein 1A) gene is located on chromosome 1p36.11 and is part of the chromatin remodeling complex SWI/SNF (switch/sucrose non-fermentable complex). By demonstrating a possible link between a decreased ARID1A protein level and the LOH 1p, as well as recurrence and a higher tumor grading in meningioma, we provide for the first time functional evidence of the LOH 1p. This may be of prognostic and therapeutic interest.
Abstract
Background/Objectives: Loss of heterozygosity (LOH) in meningioma has been known for more than two decades. It has been shown that LOH on chromosome 1p36 is an independent marker of meningioma recurrence and progression. ARID1A, a tumor suppressor gene located on chromosome 1p36.11, is part of the chromatin-regulating SWI/SNF complex whose subunits are altered in 20% of cases across all tumor entities. Methods: Using our newly developed indirect enzyme-linked immunosorbent assay (ELISA), we investigated whether tumors with or without LOH 1p differ in ARID1A expression in 61 meningiomas. To study possible links between ARID1A and ARID1B, we tested for LOH 6q in association with LOH 1p using a PCR-based microsatellite approach. ARID1B, another member of the SWI/SNF complex, is located on 6q25.3. Additionally, we compared our ELISA results with immunohistochemistry data staining of ARID1A in tissue sections known to harbor LOH 1p. Results: Our results indicate that meningiomas harboring LOH 1p have significantly lower ARID1A levels compared to tumors without LOH 1p. In free nuclear protein fractions, reductions were up to 32% (CI: 6–58.7%). Interestingly, we found that ARID1A levels were significantly lower in tumors with recurrence and/or multiple localizations. In addition, our analysis of chromosome 6q uncovered a significantly strong correlation between LOH 1p and LOH 6q (p < 0.0001). Conclusions: These results highlight the importance of ARID1A in meningioma malignization and indicate for the first time functional evidence for LOH 1p.