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A study published in Acta Neuropathologica explores the relationship between chromosome 1p loss and the risk of recurrence in meningioma, a type of brain tumor. The researchers found that losses in chromosome 1p, particularly those exceeding 5%, were associated with an increased risk of recurrence. The study also suggests that even small losses in chromosome 1p may indicate chromosomal instability and increased tumor growth. The findings highlight the importance of considering 1p loss as a marker for increased risk in meningioma, with a proposed clinically relevant cut-off of 5%. [Extracted from the article]

Aim: Pilocytic astrocytomas (PA) in adults are rare and may be challenging to identify based only on histomorphology. Compared to their paediatric counterparts, they are reportedly molecularly more diverse and associated with a worse prognosis. We aimed to describe the characteristics of adult PAs more precisely by comprehensively profiling a series of 79 histologically diagnosed adult cases (≥18 years). Methods: We performed global DNA methylation profiling and DNA and RNA panel sequencing and integrated the results with clinical data. We further compared the molecular characteristics of adult and paediatric PAs that had a significant match to one of the established PA methylation classes in the Heidelberg brain tumour classifier. Results: The mean age in our cohort was 33 years, and 43% of the tumours were located supratentorially. Based on methylation profiling, only 39% of the cases received a significant match to a PA methylation class. Sixteen per cent matched a different tumour type, and 45% had a Heidelberg classifier score <0.9 with an affiliation to diverse established methylation classes in t‐SNE analyses. Although the KIAA1549::BRAF fusion was found in 98% of paediatric PAs, this was true for only 27% of histologically defined and 55% of adult PAs defined by methylation profiling. Conclusions: A particularly high fraction of adult tumours with histological features of PA do not match current PA methylation classes, indicating ambiguous histology and an urgent need for molecular profiling. Moreover, even in adult PAs with a match to a PA methylation class, the distribution of genetic drivers differs significantly from their paediatric counterparts (p < 0.01). [ABSTRACT FROM AUTHOR]

Ependymomas encompass multiple clinically relevant tumor types based on localization and molecular profiles. Tumors of the methylation class “spinal ependymoma” (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical relevance have been described in a large, epigenetically defined series. Transcriptomic (n = 72), epigenetic (n = 225), genetic (n = 134), and clinical data (n = 112) were integrated for a detailed molecular overview on SP-EPN. Additionally, we mapped SP-EPN transcriptomes to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. The integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord revealed that SP-EPN display the highest similarities to mature adult ependymal cells. Unsupervised hierarchical clustering of transcriptomic data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype A tumors primarily carried previously known germline or sporadic NF2 mutations together with 22q loss (bi-allelic NF2 loss), resulting in decreased NF2 expression. Furthermore, they more often presented as multilocular disease and demonstrated a significantly reduced progression-free survival as compared to SP-EP subtype B. In contrast, subtype B predominantly contained samples without NF2 mutation detected in sequencing together with 22q loss (monoallelic NF2 loss). These tumors showed regular NF2 expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities. [ABSTRACT FROM AUTHOR]

In summary, genetic and epigenetic profiling identifies two broader subgroups of PPTIDs with distinct histological features and clinical course: (1) the PPTIDs with I KBTBD4 i insertions which have the methylation profile subtypes PPTID-A or PPTID-B and frequently have a small-cell morphology and an unfavourable clinical course and (2) the PPTIDs without I KBTBD4 i insertions, herein suggested to be called PPTID-C, which have a methylation profile most similar to pineocytoma and frequently show a large-cell morphology, loss of chromosome 13q, and a favourable clinical course. The presence of insertions in I KBTBD4 i , methylation class PPTID, diffuse morphology subtype and hotspot Ki67 greater than or equal to 8% were significantly associated with a worse progression-free survival (PFS) by log-rank test (Fig. [Extracted from the article]

Purpose: To investigate the structure and function of the retina after scleral buckling (SB) surgery due to macula-on rhegmatogenous retinal detachment (RRD). Methods: Twenty eyes with repaired macula-on RRD and 20 fellow eyes were included. All patients within 6–12 months of the procedure, were examined to evaluate retinal structure using spectral domain optical coherence tomography (SD-OCT) and vessel density (VD) by OCT angiography (OCTA). Best corrected visual acuity (BCVA) and microperimetry (MP) tests were used to assess retinal function. Results: Analysis of the microvascular network using OCTA between the operated and healthy fellow eyes showed a significant reduction on VD in superficial vascular plexus (SVP), deep vascular plexus (DVP) and radial peripapillary capillaries (RPC) (p< 0.001, p = 0.019 and p = 0.008, respectively). Comparison of retinal structure in SD-OCT showed no significant differences on thickness in ganglion cell complex (GCC) and peripaillary retinal nerve fiber layer (pRNFL) (p> 0.05) between examined eyes. Retinal function analysis by MP examination showed a decrease of retinal sensitivity (p = 0.0013) whereas postoperative BCVA showed no differences (p = 0.62) in the operated eyes. Significant Pearson's correlations were observed between retinal sensitivity and VD in SVP, RPC (p< 0.05). Conclusion: In the eyes after SB surgery due to macula-on RRD, changes in retinal sensitivity were accompanied by impairment of the microvascular network assessed by the OCTA. [ABSTRACT FROM AUTHOR]

Pleomorphic xanthoastrocytoma (PXA) in its classic manifestation exhibits distinct morphological features and is assigned to CNS WHO grade 2 or grade 3. Distinction from glioblastoma variants and lower grade glial and glioneuronal tumors is a common diagnostic challenge. We compared a morphologically defined set of PXA (histPXA) with an independent set, defined by DNA methylation analysis (mcPXA). HistPXA encompassed 144 tumors all subjected to DNA methylation array analysis. Sixty-two histPXA matched to the methylation class mcPXA. These were combined with the cases that showed the mcPXA signature but had received a histopathological diagnosis other than PXA. This cohort constituted a set of 220 mcPXA. Molecular and clinical parameters were analyzed in these groups. Morphological parameters were analyzed in a subset of tumors with FFPE tissue available. HistPXA revealed considerable heterogeneity in regard to methylation classes, with methylation classes glioblastoma and ganglioglioma being the most frequent mismatches. Similarly, the mcPXA cohort contained tumors of diverse histological diagnoses, with glioblastoma constituting the most frequent mismatch. Subsequent analyses demonstrated the presence of canonical pTERT mutations to be associated with unfavorable prognosis among mcPXA. Based on these data, we consider the tumor type PXA to be histologically more varied than previously assumed. Histological approach to diagnosis will predominantly identify cases with the established archetypical morphology. DNA methylation analysis includes additional tumors in the tumor class PXA that share similar DNA methylation profile but lack the typical morphology of a PXA. DNA methylation analysis also assist in separating other tumor types with morphologic overlap to PXA. Our data suggest the presence of canonical pTERT mutations as a robust indicator for poor prognosis in methylation class PXA. [ABSTRACT FROM AUTHOR]

Background: Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and current indications for postoperative radiotherapy are controversial. Recent studies have proposed prognostic meningioma classification systems using DNA methylation profiling, copy number variants, DNA sequencing, RNA sequencing, histology, or integrated models based on multiple combined features. Targeted gene expression profiling has generated robust biomarkers integrating multiple molecular features for other cancers, but is understudied for meningiomas., Methods: Targeted gene expression profiling was performed on 173 meningiomas and an optimized gene expression biomarker (34 genes) and risk score (0 to 1) was developed to predict clinical outcomes. Clinical and analytical validation was performed on independent meningiomas from 12 institutions across 3 continents (N = 1856), including 103 meningiomas from a prospective clinical trial. Gene expression biomarker performance was compared to 9 other classification systems., Results: The gene expression biomarker improved discrimination of postoperative meningioma outcomes compared to all other classification systems tested in the independent clinical validation cohort for local recurrence (5-year area under the curve [AUC] 0.81) and overall survival (5-year AUC 0.80). The increase in area under the curve compared to the current standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval [CI] 0.07-0.17, P < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% CI 0.37-0.78, P = 0.0001) and re-classified up to 52.0% meningiomas compared to conventional clinical criteria, suggesting postoperative management could be refined for 29.8% of patients., Conclusions: A targeted gene expression biomarker improves discrimination of meningioma outcomes compared to recent classification systems and predicts postoperative radiotherapy responses., Competing Interests: Conflict of Interest Notification: MP has received honoraria for lectures, consultation, or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals. WCC and DRR are the inventors on patent PCT/US 21/70288 describing the use of targeted gene expression profiling to predict meningioma outcomes and radiotherapy responses.