Project description:To assess their utility in routine neuropathology, we prospectively integrated DNA methylation-based CNS tumor classification and targeted gene panel sequencing of tumor and constitutional DNA with blinded neuropathological reference diagnostics for a population-based cohort of > 1,200 newly-diagnosed pediatric patients.
Project description:The large diversity of central nervous system (CNS) tumor types in children and adolescents results in disparate patient outcomes and renders accurate diagnosis challenging. In this study, we prospectively integrated DNA methylation profiling and targeted gene panel sequencing with blinded neuropathological reference diagnostics for a population-based cohort of more than 1,200 newly diagnosed pediatric patients with CNS tumors, to assess their utility in routine neuropathology. We show that the multi-omic integration increased diagnostic accuracy in a substantial proportion of patients through annotation to a refining DNA methylation class (50%), detection of diagnostic or therapeutically relevant genetic alterations (47%) or identification of cancer predisposition syndromes (10%). Discrepant results by neuropathological WHO-based and DNA methylation-based classification (30%) were enriched in histological high-grade gliomas, implicating relevance for current clinical patient management in 5% of all patients. Follow-up (median 2.5 years) suggests improved survival for patients with histological high-grade gliomas displaying lower-grade molecular profiles. These results provide preliminary evidence of the utility of integrating multi-omics in neuropathology for pediatric neuro-oncology.
Project description:To assess their utility in routine neuropathology, we prospectively integrated DNA methylation-based CNS tumor classification and targeted gene panel sequencing of tumor and constitutional DNA with blinded neuropathological reference diagnostics for a population-based cohort of > 1,200 newly-diagnosed pediatric patients.
Project description:Tumor heterogeneity is a major challenge for oncology drug discovery and development. Understanding of the spatial tumor landscape is key to identifying new targets and impactful model systems. Here, we test the utility of spatial transcriptomics (ST) for Oncology Discovery by profiling 40 tissue sections and 80,024 capture spots across a diverse set of tissue types, sample formats, and RNA capture chemistries. We verify the accuracy and fidelity of ST by leveraging matched pathology analysis that provide a ground truth for tissue section composition. We then use spatial data to demonstrate the capture of key tumor depth features, identifying hypoxia, necrosis, vasculature, and extracellular matrix variation. We also leverage spatial context to identify relative cell type locations showing the anti-correlation of tumor and immune cells in syngeneic cancer models. Lastly, we demonstrate target identification approaches in clinical pancreatic adenocarcinoma samples, highlighting tumor intrinsic biomarkers and paracrine signaling.
Project description:Traumatic brain injury (TBI) can lead to significant neuropsychiatric problems and neurodegenerative pathologies, which develop and persist years after injury. Neuroinflammatory processes evolve over this same period. Therefore, we aimed to determine the contribution of microglia to neuropathology at acute (1-day post-injury; dpi), subacute (7 dpi), and chronic (30 dpi) time-points. Microglia were depleted with PLX5622, a CSF1R antagonist, prior to midline fluid percussion injury in male mice and cortical neuropathology/inflammation was assessed using a neuropathology mRNA panel. NanoString Neuropathology gene expression panel was used to quantify expression from RNA microdissected from the mouse cortex.
Project description:BackgroundPatients with primary brain tumours (i.e., neuro-oncology patients) lack access to exercise oncology and wellness resources. The purpose of the Alberta Cancer Exercise - Neuro-Oncology (ACE-Neuro) study is to assess the feasibility of a tailored neuro-oncology exercise program for patients across Alberta, Canada. The primary outcome is to assess the feasibility of ACE-Neuro. The secondary outcome is to examine preliminary effectiveness of ACE-Neuro on patient-reported outcomes and functional fitness.MethodsNeuro-oncology patients with a malignant or benign primary brain tumour that are pre, on, or completed treatment, are >18 years, and able to consent in English are eligible to participate in the study. Following referral from the clinical team to cancer rehabilitation and the study team, participants are triaged to determine their appropriateness for ACE-Neuro and other cancer rehabilitation services (including physiatry, physiotherapy, occupational therapy, and exercise physiology). In ACE-Neuro, participants complete a tailored 12-week exercise program with pre-post assessments of patient-reported outcomes and functional fitness, and objective physical activity tracked across the 12-week program. ACE-Neuro includes individual and group-based exercise sessions, as well as health coaching.ConclusionWe are supporting ACE-Neuro implementation into clinical cancer care, with assessment of needs enabling a tailored exercise prescription.