Transcriptomic observations of intra and extracellular immunotherapy targets for pediatric brain tumors.

Objectives: Despite surgical resection, chemoradiation, and targeted therapy, brain tumors remain a leading cause of cancer-related death in children. Immunotherapy has shown some promise and is actively being investigated for treating childhood brain tumors. However, a critical step in advancing immunotherapy for these patients is to uncover targets that can be effectively translated into therapeutic interventions.

A multi-institutional pediatric dataset of clinical radiology MRIs by the Children's Brain Tumor Network.

Pediatric brain and spinal cancers remain the leading cause of cancer-related death in children. Advancements in clinical decision-support in pediatric neuro-oncology utilizing the wealth of radiology imaging data collected through standard care, however, has significantly lagged other domains. Such data is ripe for use with predictive analytics such as artificial intelligence (AI) methods, which require large datasets.

Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial.

OpenPBTA: The Open Pediatric Brain Tumor Atlas.

Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Children's Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to establish OpenPBTA, an open collaborative project with over 40 scalable analysis modules that genomically characterize 1,074 pediatric brain tumors.

The Brain Tumor Segmentation (BraTS) Challenge 2023: .

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations.

Optical genome mapping identifies a novel pediatric embryonal tumor with a ZNF532::NUTM1 fusion.

The molecular characteristics of pediatric brain tumors have not only allowed for tumor subgrouping but have led to the introduction of novel treatment options for patients with specific tumor alterations. Therefore, an accurate histologic and molecular diagnosis is critical for optimized management of all pediatric patients with brain tumors, including central nervous system embryonal tumors. We present a case where optical genome mapping identified a ZNF532::NUTM1 fusion in a patient with a unique tumor best characterized histologically as a central nervous system embryonal tumor with rhabdoid features.

Cellular Therapy for Children with Central Nervous System Tumors: Mining and Mapping the Correlative Data.

Purpose Of Review: Correlative studies should leverage clinical trial frameworks to conduct biospecimen analyses that provide insight into the bioactivity of the intervention and facilitate iteration toward future trials that further improve patient outcomes. In pediatric cellular immunotherapy trials, correlative studies enable deeper understanding of T cell mobilization, durability of immune activation, patterns of toxicity, and early detection of treatment response. Here, we review the correlative science in adoptive cell therapy (ACT) for childhood central nervous system (CNS) tumors, with a focus on existing chimeric antigen receptor (CAR) and T cell receptor (TCR)-expressing T cell therapies.

Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.

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.

The children's brain tumor network (CBTN) - Accelerating research in pediatric central nervous system tumors through collaboration and open science.

Pediatric brain tumors are the leading cause of cancer-related death in children in the United States and contribute a disproportionate number of potential years of life lost compared to adult cancers. Moreover, survivors frequently suffer long-term side effects, including secondary cancers. The Children's Brain Tumor Network (CBTN) is a multi-institutional international clinical research consortium created to advance therapeutic development through the collection and rapid distribution of biospecimens and data via open-science research platforms for real-time access and use by the global research community.

OLIG2 Is a Determinant for the Relapse of MYC-Amplified Medulloblastoma.

Purpose: Patients with MYC-amplified medulloblastoma (MB) have poor prognosis and frequently develop recurrence, thus new therapeutic approaches to prevent recurrence are needed.

Experimental Design: We evaluated OLIG2 expression in a panel of mouse Myc-driven MB tumors, patient MB samples, and patient-derived xenograft (PDX) tumors and analyzed radiation sensitivity in OLIG2-high and OLIG2-low tumors in PDX lines. We assessed the effect of inhibition of OLIG2 by OLIG2-CRISPR or the small molecule inhibitor CT-179 combined with radiotherapy on tumor progression in PDX models.

Proteogenomic discovery of neoantigens facilitates personalized multi-antigen targeted T cell immunotherapy for brain tumors.

Neoantigen discovery in pediatric brain tumors is hampered by their low mutational burden and scant tissue availability. Here we develop a proteogenomic approach combining tumor DNA/RNA sequencing and mass spectrometry proteomics to identify tumor-restricted (neoantigen) peptides arising from multiple genomic aberrations to generate a highly target-specific, autologous, personalized T cell immunotherapy. Our data indicate that aberrant splice junctions are the primary source of neoantigens in medulloblastoma, a common pediatric brain tumor.

Associations Between Social Support Availability and HIV Risk and Protective Factors in a U.S. Sample of Adults with Diverse Transgender Identities.

There is conflicting evidence on how different types of social support may attenuate human immunodeficiency virus (HIV) risk or may even promote health behaviors in transgender (trans) and nonbinary populations. Drawing on Social Support Theory, we assessed associations between emotional, instrumental, and informational social support and HIV risk and protective factors in a U.S.

Integrated Proteogenomic Characterization across Major Histological Types of Pediatric Brain Cancer.

We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA sequencing, and proteomics and phosphoproteomics profiling, of 218 tumors across 7 histological types of childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade glioma (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16), and atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological themes that span histological boundaries, suggesting that treatments used for one histological type may be applied effectively to other tumors sharing similar proteomics features. Immune landscape characterization reveals diverse tumor microenvironments across and within diagnoses.

(Hypermethylated in Cancer 1) modulates the contractile activity of prostate stromal fibroblasts and directly regulates expression.

() a tumor suppressor gene located at 17p13.3, is frequently deleted or epigenetically silenced in many human tumors. encodes a transcriptional repressor involved in various aspects of the DNA damage response and in complex regulatory loops with P53 and SIRT1.

Harmonization of postmortem donations for pediatric brain tumors and molecular characterization of diffuse midline gliomas.

Children diagnosed with brain tumors have the lowest overall survival of all pediatric cancers. Recent molecular studies have resulted in the discovery of recurrent driver mutations in many pediatric brain tumors. However, despite these molecular advances, the clinical outcomes of high grade tumors, including H3K27M diffuse midline glioma (H3K27M DMG), remain poor.

Correction to: Comparative multidimensional molecular analyses of pediatric diffuse intrinsic pontine glioma reveals distinct molecular subtypes.

The original version of this article unfortunately contained a mistake.

Social and Medical Gender Affirmation Experiences Are Inversely Associated with Mental Health Problems in a U.S. Non-Probability Sample of Transgender Adults.

A dearth of research has explored concurrently the associations between multiple forms of gender affirmation (or transitioning) and the mental health of transgender adults. In 2015, 288 U.S.

Implications of new understandings of gliomas in children and adults with NF1: report of a consensus conference.

Gliomas are the most common primary central nervous system tumors occurring in children and adults with neurofibromatosis type 1 (NF1). Over the past decade, discoveries of the molecular basis of low-grade gliomas (LGGs) have led to new approaches for diagnosis and treatments. However, these new understandings have not been fully applied to the management of NF1-associated gliomas.

Germline microsatellite genotypes differentiate children with medulloblastoma.

Background: The germline genetic events underpinning medulloblastoma (MB) initiation, and therefore the ability to determine who is at risk, are still unknown for the majority of cases. Microsatellites are short repeated sequences that make up ~3% of the genome. Repeat lengths vary among individuals and are often nonrandomly associated with disease, including several cancers such as breast, glioma, lung, and ovarian.

Drives Group 3 Medulloblastoma through Transformation of Sox2 Astrocyte Progenitor Cells.

A subset of group 3 medulloblastoma frequently harbors amplification or overexpression of lacking additional focal aberrations, yet it remains unclear whether overexpression alone can induce tumorigenesis and which cells give rise to these tumors. Here, we showed that astrocyte progenitors in the early postnatal cerebellum were susceptible to transformation by . The resulting tumors specifically resembled human group 3 medulloblastoma based on histology and gene-expression profiling.

Proteomic analysis of Medulloblastoma reveals functional biology with translational potential.

Genomic characterization has begun to redefine diagnostic classifications of cancers. However, it remains a challenge to infer disease phenotypes from genomic alterations alone. To help realize the promise of genomics, we have performed a quantitative proteomics investigation using Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and 41 tissue samples spanning the 4 genomically based subgroups of medulloblastoma and control cerebellum.

Minority Stressors Associated with Sexual Risk Behaviors and HIV Testing in a U.S. Sample of Transgender Individuals.

The majority of published research on transgender health focuses on associations between external minority stressors (e.g., discrimination) and health.

Identity concealment in transgender adults: A qualitative assessment of minority stress and gender affirmation.

Minority individuals might conceal their identity in social contexts in an effort to avoid stigma and victimization. Unfortunately, identity concealment is thought to impact psychological distress in transgender and gender nonconforming (TGNC) individuals. Thus, through 30 in-depth interviews, we sought to understand if and how identity concealment was experienced by TGNC individuals.