High-grade meningiomas make up a relatively minor proportion of meningiomas, which are one of the most common types of primary intracranial tumors in adults. Though rare, a considerable portion of highgrade meningiomas arise from malignant transformation of benign meningiomas. The 2021 World Health Organization (WHO) classification criteria introduced molecular markers in the diagnosis and grading of central nervous system (CNS) tumors and assigned certain genomic mutations to grade 3 meningiomas. We report a case of a 54-year-old male patient who underwent stepwise malignant transformation of meningioma from WHO grade 1 to grade 3 within 10 years, during the course of five surgeries followed by adjuvant stereotactic radiosurgery and radiotherapy. We performed next-generation sequencing (NGS) on the most recent grade 3 meningioma specimen and found that it carried a telomerase reverse transcriptase promoter (TERTp) mutation (c.-124C>T) in accordance with the 2021 WHO criteria for grade 3 meningiomas. We then retrospectively examined the previous grade 1 and 2 specimens and found them to have the same mutation. We reviewed the significance of molecular markers in the diagnosis of meningiomas, possible genetic alterations associated with their malignant transformation, and what measures could be taken to effectively manage meningiomas considering NGS findings.

High-grade meningiomas make up a relatively minor proportion of meningiomas, which are one of the most common types of primary intracranial tumors in adults. Though rare, a considerable portion of highgrade meningiomas arise from malignant transformation of benign meningiomas. The 2021 World Health Organization (WHO) classification criteria introduced molecular markers in the diagnosis and grading of central nervous system (CNS) tumors and assigned certain genomic mutations to grade 3 meningiomas. We report a case of a 54-year-old male patient who underwent stepwise malignant transformation of meningioma from WHO grade 1 to grade 3 within 10 years, during the course of five surgeries followed by adjuvant stereotactic radiosurgery and radiotherapy. We performed next-generation sequencing (NGS) on the most recent grade 3 meningioma specimen and found that it carried a telomerase reverse transcriptase promoter (TERTp) mutation (c.-124C>T) in accordance with the 2021 WHO criteria for grade 3 meningiomas. We then retrospectively examined the previous grade 1 and 2 specimens and found them to have the same mutation. We reviewed the significance of molecular markers in the diagnosis of meningiomas, possible genetic alterations associated with their malignant transformation, and what measures could be taken to effectively manage meningiomas considering NGS findings.

High-grade meningiomas make up a relatively minor proportion of meningiomas, which are one of the most common types of primary intracranial tumors in adults. Though rare, a considerable portion of highgrade meningiomas arise from malignant transformation of benign meningiomas. The 2021 World Health Organization (WHO) classification criteria introduced molecular markers in the diagnosis and grading of central nervous system (CNS) tumors and assigned certain genomic mutations to grade 3 meningiomas. We report a case of a 54-year-old male patient who underwent stepwise malignant transformation of meningioma from WHO grade 1 to grade 3 within 10 years, during the course of five surgeries followed by adjuvant stereotactic radiosurgery and radiotherapy. We performed next-generation sequencing (NGS) on the most recent grade 3 meningioma specimen and found that it carried a telomerase reverse transcriptase promoter (TERTp) mutation (c.-124C>T) in accordance with the 2021 WHO criteria for grade 3 meningiomas. We then retrospectively examined the previous grade 1 and 2 specimens and found them to have the same mutation. We reviewed the significance of molecular markers in the diagnosis of meningiomas, possible genetic alterations associated with their malignant transformation, and what measures could be taken to effectively manage meningiomas considering NGS findings.

High-grade meningiomas make up a relatively minor proportion of meningiomas, which are one of the most common types of primary intracranial tumors in adults. Though rare, a considerable portion of highgrade meningiomas arise from malignant transformation of benign meningiomas. The 2021 World Health Organization (WHO) classification criteria introduced molecular markers in the diagnosis and grading of central nervous system (CNS) tumors and assigned certain genomic mutations to grade 3 meningiomas. We report a case of a 54-year-old male patient who underwent stepwise malignant transformation of meningioma from WHO grade 1 to grade 3 within 10 years, during the course of five surgeries followed by adjuvant stereotactic radiosurgery and radiotherapy. We performed next-generation sequencing (NGS) on the most recent grade 3 meningioma specimen and found that it carried a telomerase reverse transcriptase promoter (TERTp) mutation (c.-124C>T) in accordance with the 2021 WHO criteria for grade 3 meningiomas. We then retrospectively examined the previous grade 1 and 2 specimens and found them to have the same mutation. We reviewed the significance of molecular markers in the diagnosis of meningiomas, possible genetic alterations associated with their malignant transformation, and what measures could be taken to effectively manage meningiomas considering NGS findings.

Capicua (CIC) is a transcriptional repressor that regulates several developmental processes. CIC deficiency results in lymphoproliferative autoimmunity accompanied by expansion of CD44hiCD62Llo effector/memory and follicular Th cell populations. Deletion of Cic alleles in hematopoietic stem cells (Vav1-Cre-mediated knockout of Cic) causes more severe autoimmunity than that caused by the knockout of Cic in CD4+CD8+ double positive thymocytes (Cd4-Cre-mediated knockout of Cic). In this study, we compared splenic CD4+ T cell activation and proliferation between whole immune cell-specific Cic-null (Cicf/f;Vav1-Cre) and T cell-specific Cic-null (Cicf/f;Cd4-Cre) mice. Hyperactivation and hyperproliferation of CD4+ T cells were more apparent in Cicf/f;Vav1-Cre mice than in Cicf/f;Cd4-Cre mice. Cicf/f;Vav1-Cre CD4+ T cells more rapidly proliferated and secreted larger amounts of IL-2 upon TCR stimulation than did Cicf/f;Cd4-Cre CD4+ T cells, while the TCR stimulation-induced activation of the TCR signaling cascade and calcium flux were comparable between them. Mixed wild-type and Cicf/f;Vav1-Cre bone marrow chimeras also exhibited more apparent hyperactivation and hyperproliferation of Cic-deficient CD4+ T cells than did mixed wild-type and Cicf/f;Cd4-Cre bone marrow chimeras. Taken together, our data demonstrate that CIC deficiency at the beginning of T cell development endows peripheral CD4+ T cells with enhanced T cell activation and proliferative capability.