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Mutational Analysis of Recurrent Meningioma Progressing From Atypical to Rhabdoid Subtype
Mateusz Bujko1, Marcin M Machnicki2, Emilia Grecka1
1Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Background:
Rhabdoid meningioma is rare aggressive meningioma histological subtype that develops predominantly through progression from less malignant tumors. Owing to its low incidence, this tumor's biological background is unknown. The aim of this study was to profile somatic mutations in 4 meningioma samples from the same patient, derived previously from 4 subsequent tumor resections.
Case Description:
A 58-year-old woman presented with recurrent meningioma progressing from atypical to rhabdoid subtype. Four tumor samples that represent a primary tumor (atypical GII) and 3 recurrent tumors that were subsequently removed (anaplastic GIII, rhabdoid GIII, and anaplastic/rhabdoid GIII) from this patient were subjected to mutational analysis of coding sequences of 952 tumor-related genes. Three mutations were identified in all tumor samples exhibiting a high allelic frequency: ARID1A frameshift deletion, NF2 in-frame deletion, and missense variant of SRSF2. The predicted inactivating effect of ARID1A deletion was confirmed by immunohistochemical staining of tumor sections in which a high proportion of cells lacked protein expression. Additional low-allelic-fraction mutations were observed in all tumor samples, likely representing "passenger," low-effect mutations that reflect a clonal selection of tumor cells through malignant progression of the meningioma.
Conclusion:
The mutation of ARID1A that encodes the subunit of the SWI/SNF complex represents the most likely driver of the tumor's malignant potential. It also may be involved in the acquisition of the rhabdoid phenotype, given that mutations in chromatin remodeling proteins are the hallmark of atypical teratoid/rhabdoid tumors.
Insights
Somatic mutation analysis of aggressive rhabdoid meningioma revealed ARID1A as a likely driver mutation. This finding offers insight into the tumor's malignant progression and rhabdoid phenotype acquisition.
Area of Science:
- Neuro-oncology
- Cancer Genomics
- Tumor Progression
Background:
- Rhabdoid meningioma is a rare, aggressive subtype, often arising from less malignant precursors.
- The biological underpinnings of rhabdoid meningioma remain largely unknown due to its low incidence.
- This study aimed to profile somatic mutations in sequential tumors from a single patient.
Observation:
- A patient with recurrent meningioma showed progression from atypical (GII) to anaplastic and rhabdoid (GIII) subtypes.
- Four distinct tumor samples (primary and three recurrences) were analyzed for mutations in 952 tumor-related genes.
- ARID1A frameshift deletion, NF2 in-frame deletion, and SRSF2 missense variant were identified in all samples with high allelic frequency.
Findings:
- ARID1A deletion, predicted to inactivate the protein, was confirmed via immunohistochemistry showing loss of protein expression.
- The identified ARID1A mutation is the most probable driver of the tumor's malignant potential.
- Mutations in chromatin remodeling proteins, like ARID1A, are characteristic of atypical teratoid/rhabdoid tumors.
Implications:
- ARID1A mutations may play a critical role in the development of the rhabdoid phenotype in meningioma.
- Understanding these genetic drivers can inform future therapeutic strategies for aggressive meningiomas.
- This case study provides valuable insights into the clonal evolution and molecular pathogenesis of rhabdoid meningioma.
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