RESUMEN
BACKGROUND: Although meningioma is the most common primary brain tumor, treatments rely on surgery and radiotherapy, and recurrent meningiomas have no standard therapeutic options due to a lack of clinically relevant research models. Current meningioma cell lines or organoids cannot reflect biological features of patient tumors since they undergo transformation along culture and consist of only tumor cells without microenvironment. We aim to establish patient-derived meningioma organoids (MNOs) preserving diverse cell types representative of the tumor microenvironment. METHODS: The biological features of MNOs were evaluated using WST, LDH, and collagen-based 3D invasion assays. Cellular identities in MNOs were confirmed by immunohistochemistry (IHC). Genetic alteration profiles of MNOs and their corresponding parental tumors were obtained by whole-exome sequencing. RESULTS: MNOs were established from four patients with meningioma (two grade 1 and two grade 2) at a 100% succession rate. Exclusion of enzymatic dissociation-reaggregation steps endowed MNOs with original histology and tumor microenvironment. In addition, we used a liquid media culture system instead of embedding samples into Matrigel, resulting in an easy-to-handle, cost-efficient, and time-saving system. MNOs maintained their functionality and morphology after long-term culture (> 9 wk) and repeated cryopreserving-recovery cycles. The similarities between MNOs and their corresponding parental tumors were confirmed by both IHC and whole-exome sequencing. As a representative application, we utilized MNOs in drug screening, and mifepristone, an antagonist of progesterone receptor, showed prominent antitumor efficacy with respect to viability, invasiveness, and protein expression. CONCLUSION: Taken together, our MNO model overcame limitations of previous meningioma models and showed superior resemblance to parental tumors. Thus, our model could facilitate translational research identifying and selecting drugs for meningioma in the era of precision medicine.
RESUMEN
PURPOSE: For asymptomatic non-functioning pituitary adenomas (NFPAs), conservative approaches such as observation are preferred. However, some NFPAs exhibit poor prognoses. Thus, the purpose of this study was to investigate clinicopathological characteristics of tumors for identifying those with unfavorable prognoses. METHODS: A total of 125 patients with NFPAs who underwent surgery between November 2017 and December 2022 at our institution were retrospectively analyzed. Clinical, radiological, and pathological data, including hormone profiles, tumor size, presence of cavernous sinus invasion, and Ki-67 index levels, were reviewed. High-risk PAs were identified according to 2022 WHO criteria. Statistical analyses including Kaplan-Meier survival analysis and Cox regression were performed to evaluate factors associated with tumor progression or recurrence. RESULTS: A high-risk group demonstrated a significantly higher rate of tumor progression/recurrence than a low-risk group (p-value = 0.004). In multivariate analysis, the high-risk group at the time of diagnosis remained as an independent prognostic factor for NFPAs (p-value = 0.0148). The high-risk group also had a higher percentage of younger patients (80.0% in the high-risk group vs. 62.2% in the low-risk group, p-value = 0.016) and female patients (91.4% vs. 34.4%, p< 0.001). The presence of cavernous sinus invasion and higher Ki-67 index levels were more commonly observed in the high-risk group, although these factors did not significantly impact the overall prognosis. CONCLUSION: Our findings indicate that patients with high-risk NFPAs have a more aggressive disease course and a higher rate of progression or recurrence. This high-risk group has higher prevalence of younger and female patients. They may benefit from closer monitoring and possibly more aggressive treatment approaches.
RESUMEN
BACKGROUND: Glioma is caused by multiple genomic alterations. The evolving classification of gliomas emphasizes the significance of molecular testing. Next generation sequencing (NGS) offers the assessment of parallel combinations of multiple genetic alterations and identifying actionable mutations that guide treatment. This study comprehensively analyzed glioma patients using multi-gene NGS panels, providing powerful insights to inform diagnostic classification and targeted therapies. METHODS: We conducted a targeted panel-based NGS analysis on formalin-fixed and paraffin-embedded nucleic acids extracted from a total of 147 glioma patients. These samples underwent amplicon capture-based library preparation and sequenced using the Oncomine Comprehensive Assay platform. The resulting sequencing data were then analyzed using the bioinformatics tools. RESULTS: A total of 301 mutations, were found in 132 out of 147 tumors (89.8%). These mutations were in 68 different genes. In 62 tumor samples (42.2%), copy number variations (CNVs) with gene amplifications occurred in 25 genes. Moreover, 25 tumor samples (17.0%) showed gene fusions in 6 genes and intragenic deletion in a gene. Our analysis identified actionable targets in several genes, including 11 with mutations, 8 with CNVs, and 3 with gene fusions and intragenic deletion. These findings could impact FDA-approved therapies, NCCN guideline-based treatments, and clinical trials. CONCLUSION: We analyzed precisely diagnosing the classification of gliomas, detailing the frequency and co-occurrence of genetic alterations and identifying genetic alterations with potential therapeutic targets by NGS-based molecular analysis. The high-throughput NGS analysis is an efficient and powerful tool to comprehensively support molecular testing in neurooncology.