A5005300416- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- CAR-T cell therapy research
- Erythrocyte Function and Pathophysiology
- Genomics and Rare Diseases
- Cancer Research and Treatments
- Metabolism and Genetic Disorders
- Cancer Cells and Metastasis
- RNA Interference and Gene Delivery
- 14-3-3 protein interactions
- RNA Research and Splicing
- Cytokine Signaling Pathways and Interactions
- Hedgehog Signaling Pathway Studies
- Single-cell and spatial transcriptomics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Protein Degradation and Inhibitors
- DNA Repair Mechanisms
- Chronic Myeloid Leukemia Treatments
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Immune cells in cancer
- Cancer-related gene regulation
SickKids Foundation
2012-2025
University of Toronto
2012-2025
Hospital for Sick Children
2012-2025
University Health Network
2016-2025
Princess Margaret Cancer Centre
2016-2025
Occupational Cancer Research Centre
2014
First Hospital of Jilin University
2013
Jilin University
2013
University of Portsmouth
2013
Washington University in St. Louis
2013
Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT medulloblastoma have not been described. Hence, we sought describe these their impact a subgroup-specific manner. We analyzed by direct sequencing genotyping 466 medulloblastomas. The mutational distributions determined according subgroup affiliation, demographics, clinical,...
Replicative immortality is a hallmark of cancer cells governed by telomere maintenance. Approximately 90% human cancers maintain their telomeres activating telomerase, driven the transcriptional upregulation telomerase reverse transcriptase (TERT). Although TERT promoter mutations (TPMs) are major cancer-associated genetic mechanism upregulation, many exhibit without TPMs. In this study, we describe hypermethylated oncological region (THOR), 433-bp genomic encompassing 52 CpG sites located...
Abstract Disease recurrence causes significant mortality in B-progenitor acute lymphoblastic leukemia (B-ALL). Genomic analysis of matched diagnosis and relapse samples shows often arising from minor subclones. However, why therapy eradicates some subclones while others survive progress to remains obscure. Elucidation mechanisms underlying these differing fates requires functional isolated Here, large-scale limiting dilution xenografting samples, combined with targeted sequencing, identified...
Abstract Glioblastoma growth is driven by cancer cells that have stem cell properties, but molecular determinants of their tumorigenic behavior are poorly defined. In cancer, altered activity the epigenetic modifiers Polycomb and Trithorax complexes may contribute to neoplastic phenotype. Here, we provide first mechanistic insights into role protein mixed lineage leukemia (MLL) in maintaining characteristics human glioblastoma. We found MLL directly activates Homeobox gene HOXA10. turn,...
Medulloblastoma (MB) is a neoplasm linked to dysregulated cerebellar development. Previously, we demonstrated that the Sonic Hedgehog (SHH) subgroup grows hierarchically, with Sox2+ cells at apex of tumor progression and relapse. To test whether this mechanism rooted in normal developmental process, studied role Sox2 We find external germinal layer (EGL) derived from embryonic precursors EGL maintains rare fraction during first postnatal week. Through lineage tracing single-cell analysis,...
<p>Prevalence of CHIP variants across cohorts and association with age. <b>A,</b> Percentage patients in each cohort. Insert shows the breakdown by tumor type PREDiCT-l <b>B,</b> Number a variant gene; <i>DNMT3A</i>, <i>TET2</i>, <i>ASXL1</i>. <b>C,</b> Protein position coding gene. Each lollipop represents patient, multiple dots show same position, red outlines high impact (frameshift or stop gain). Orange bars...
<p>Consort diagram and reasons for exclusion.</p>
<p>CHIP and adverse events. <b>A,</b> Percentage of patients on each treatment that had an event therapy, split by cohort treatment. <b>B,</b> Proportions with events CHIP status. Lighter shades indicate no event, darker event. <i>P</i> values were determined Fisher exact tests.</p>
<p>Progression free survival for patients on PREDiCT-l, split by tumor type. Therapy received is indicated in each title above Kaplan Meier curve.</p>
<p>TRIPOD checklist</p>
<p>CHIP and treatment outcomes. Kaplan–Meier curves showing the difference in outcome between patients with (CHIP+) without CHIP (CHIP−) outcomes on different therapies. PFS is shown left two columns for all three cohorts, OS right CO.26 (top row) PA.7 (middle row). Hazard ratios displayed are derived from univariable Cox proportional hazards models, interaction <i>P</i> values multivariable models (see “Materials Methods”).</p>
<p>VAF of all CHIP variants split by cohort</p>
<div>Abstract<p>Clonal hematopoiesis of indeterminate potential (CHIP) is the clonal expansion hematopoietic stem cells from somatic mutations. It a common incidental finding in cell-free DNA (cfDNA). We investigated incidence CHIP cfDNA patients with solid tumors and explored its association treatment outcomes adverse events. reviewed results local prospective tumor cohort (PREDiCT-l) two randomized trials: Canadian Cancer Trials Group CO.26 [durvalumab + tremelimumab (D T) or...
<p>All CHIP variants identified in the study</p>
<p>Baseline characteristics of the included patients</p>
Clonal hematopoiesis (CH)-the expansion of somatically mutated hematopoietic cells-is common in solid cancers. CH is associated with systemic inflammation, but its impact on tumor biology underexplored. Here, we report the effects microenvironment (TME) using 1,550 treatment-naive patient samples from Clinical Proteomics Tumor Analysis Consortium (CPTAC) cohort. present 18.3% patients, one-third mutations also detectable tumor-derived DNA same individual (CH-Tum), reflecting CH-mutant...
Ten-Eleven Translocation-2 (TET2) mutations drive the expansion of mutant hematopoietic stem cells (HSCs) in clonal hematopoiesis (CH). However, precise mechanisms by which TET2 confer a competitive advantage to HSCs remain unclear. Here, through an epigenetic drug screen, we discover that inhibition disruptor telomeric silencing 1-like (DOT1L), H3K79 methyltransferase, selectively reduces fitness Tet2 knockout (Tet2KO) and progenitor (HSPCs). Mechanistically, find deficiency increases...