Fluorescence and immune-cell infiltration of nonneoplastic, postbrachytherapy brain tissue in 5-ALA-guided resection of recurrent anaplastic meningioma: illustrative case.

Background: 5-Aminolevulinic acid (5-ALA) fluorescence-guided surgery is a well-established technique for resecting high-grade gliomas. However, its application in meningiomas, especially those previously treated with radiation therapy, remains under investigation.

Observations: A 48-year-old female with recurrent anaplastic meningioma, World Health Organization grade 3, underwent a right-sided craniotomy using off-label 5-ALA as a surgical adjunct.

Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas.

Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO.

Virtual Surgical Planning of Superior Orbital Rim Fractures in Calvarial and Maxillofacial Trauma.

Background: Superior orbital rim fractures are challenging fractures as they often concomitantly occur with additional calvaria fractures. Virtual surgical planning (VSP) has been underutilized in this area of craniomaxillofacial trauma for reconstruction.

Purpose: The purpose of this study is to qualitatively describe the use of VSP and anatomically perfected stereolithic models in treatment of superior orbital rim fractures in combined neurosurgery/oral and maxillofacial surgery cases.

Genetic variation associated with condensate dysregulation in disease.

A multitude of cellular processes involve biomolecular condensates, which has led to the suggestion that diverse pathogenic mutations may dysregulate condensates. Although proof-of-concept studies have identified specific mutations that cause condensate dysregulation, the full scope of the pathological genetic variation that affects condensates is not yet known. Here, we comprehensively map pathogenic mutations to condensate-promoting protein features in putative condensate-forming proteins and find over 36,000 pathogenic mutations that plausibly contribute to condensate dysregulation in over 1,200 Mendelian diseases and 550 cancers.

Partitioning of cancer therapeutics in nuclear condensates.

The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target.

Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas.

Objective: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts.

Extent of Resection Versus Molecular Classification: What Matters When?

For malignant gliomas, the survival benefit of new combination therapies after surgical resection is measured in weeks to months. In contrast, optimizing treatment for low-grade gliomas can potentially provide additional years of life. The relatively indolent but not benign clinical course provides the opportunity for clinicians and scientists to focus not only on the duration of survival, but also to maximize quality of life.

Integrated genomic analyses of de novo pathways underlying atypical meningiomas.

This corrects the article DOI: 10.1038/ncomms14433.

Integrated genomic analyses of de novo pathways underlying atypical meningiomas.

Meningiomas are mostly benign brain tumours, with a potential for becoming atypical or malignant. On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations.

Longitudinal analysis of treatment-induced genomic alterations in gliomas.

Background: Glioblastoma multiforme (GBM) constitutes nearly half of all malignant brain tumors and has a median survival of 15 months. The standard treatment for these lesions includes maximal resection, radiotherapy, and chemotherapy; however, individual tumors display immense variability in their response to these approaches. Genomic techniques such as whole-exome sequencing (WES) provide an opportunity to understand the molecular basis of this variability.

Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas.

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.

Integrated genomic characterization of IDH1-mutant glioma malignant progression.

Gliomas represent approximately 30% of all central nervous system tumors and 80% of malignant brain tumors. To understand the molecular mechanisms underlying the malignant progression of low-grade gliomas with mutations in IDH1 (encoding isocitrate dehydrogenase 1), we studied paired tumor samples from 41 patients, comparing higher-grade, progressed samples to their lower-grade counterparts. Integrated genomic analyses, including whole-exome sequencing and copy number, gene expression and DNA methylation profiling, demonstrated nonlinear clonal expansion of the original tumors and identified oncogenic pathways driving progression.

Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene.

As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole-exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.

Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.

We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas.

Optimal surgical management of well-differentiated thyroid cancer arising in struma ovarii: a series of 4 patients and a review of 53 reported cases.

Background: Well-differentiated thyroid cancer arising in struma ovarii is rare. The optimal management of this entity remains undefined. Unilateral cystectomy, unilateral salpingo-oophorectomy (USO), or total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH/BSO), in addition to total thyroidectomy and radioactive iodine (RAI) ablation, have been employed by various groups.

Temporal requirement of the alternative-splicing factor Sfrs1 for the survival of retinal neurons.

Alternative splicing is the primary mechanism by which a limited number of protein-coding genes can generate proteome diversity. We have investigated the role of the alternative-splicing factor Sfrs1, an arginine/serine-rich (SR) protein family member, during mouse retinal development. Loss of Sfrs1 function during embryonic retinal development had a profound effect, leading to a small retina at birth.