Ledia Brunga
A5017749408- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- HIV Research and Treatment
- Genomic variations and chromosomal abnormalities
- Immunodeficiency and Autoimmune Disorders
- Cancer-related gene regulation
- Genetics and Neurodevelopmental Disorders
- Hedgehog Signaling Pathway Studies
- Virus-based gene therapy research
- DNA Repair Mechanisms
- RNA modifications and cancer
- Genomics and Rare Diseases
- Childhood Cancer Survivors' Quality of Life
- Genetic factors in colorectal cancer
- Acute Lymphoblastic Leukemia research
- Chronic Lymphocytic Leukemia Research
- Cancer and Skin Lesions
- Sarcoma Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Ethics and Legal Issues in Pediatric Healthcare
- Tumors and Oncological Cases
- Chronic Myeloid Leukemia Treatments
- Neurofibromatosis and Schwannoma Cases
- Diet and metabolism studies
Hospital for Sick Children
2017-2024
University of Toronto
2017-2023
SickKids Foundation
2017-2022
Mohammed Bin Rashid University of Medicine and Health Sciences
2017
Newcastle University
2017
British Columbia Children's Hospital
2017
Memorial University of Newfoundland
2017
Systems, Applications & Products in Data Processing (Canada)
2015
Looping together genes in cancer A subset of human cancers are characterized by aberrant fusion two specific genes. In some cases, the activity resultant protein drives tumor growth. Most appear to arise from simple reciprocal chromosomal translocations. Anderson et al. found that characteristic gene a bone and soft tissue called Ewing sarcoma is produced far more complicated mechanism (see Perspective Imielinski Ladanyi). nearly half tumors examined, was created formation dramatic genomic...
We conducted integrative somatic-germline analyses by deeply sequencing 864 cancer-associated genes, complete genomes and transcriptomes for 300 mostly previously treated children adolescents/young adults with cancer of poor prognosis or rare tumors enrolled in the SickKids Cancer Sequencing (KiCS) program. Clinically actionable variants were identified 56% patients. Improved diagnostic accuracy led to modified management a subset. Therapeutically targetable (54% patients) unanticipated...
Although replication repair deficiency, either by mismatch deficiency (MMRD) and/or loss of DNA polymerase proofreading, can cause hypermutation in cancer, microsatellite instability (MSI) is considered a hallmark MMRD alone. By genome-wide analysis tumors with germline and somatic deficiencies repair, we reveal novel association between proofreading MSI, especially when both components are lost. Analysis indels microsatellites (MS-indels) identified five distinct signatures (MS-sigs)....
People with Li-Fraumeni syndrome (LFS) harbor a germline pathogenic variant in the TP53 tumor suppressor gene, face near 100% lifetime risk of cancer, and routinely undergo intensive surveillance protocols. Liquid biopsy has become an attractive tool for range clinical applications, including early cancer detection. Here, we provide proof-of-principle multimodal liquid assay that integrates targeted gene panel, shallow whole-genome, cell-free methylated DNA immunoprecipitation sequencing...
Abstract TP53 missense mutations leading to the expression of mutant p53 oncoproteins are frequent driver events during tumorigenesis. mutants promote tumor growth, metastasis and chemoresistance by affecting fundamental cellular pathways functions. Here, we demonstrate that modify structure function Golgi apparatus, culminating in increased release a pro-malignant secretome cells primary fibroblasts from patients with Li-Fraumeni cancer predisposition syndrome. Mechanistically, interacting...
The causes of pediatric cancers' distinctiveness compared to adult-onset tumors the same type are not completely clear and fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach derive molecular definitions for most childhood cancers. Applying method 13,313 transcriptomes, constructed a cancer atlas explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due common lineages, drivers or stemness profiles. Some...
PurposeVariants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy males and females. We aimed to investigate sex-specific differences.MethodsWe collected the data of 37 unpublished patients (18 19 females) IQSEC2 pathogenic variants 5 individuals unknown significance reviewed published variants. compared variant types phenotypes females performed an analysis isoforms.ResultsIQSEC2 mainly led premature truncation were scattered throughout...
Prompt recognition of a child with cancer predisposition syndrome (CPS) has implications for management, surveillance, genetic counseling, and cascade testing relatives. Diagnosis CPS requires practitioner expertise, access to testing, test result interpretation. This diagnostic process is not accessible in all institutions worldwide, leading missed diagnoses. Advances electronic health technology can facilitate risk assessment.To evaluate the accuracy prediction tool (McGill Interactive...
PURPOSE Diagnosis of Mismatch Repair Deficiency (MMRD) is crucial for tumor management and early detection in patients with the cancer predisposition syndrome constitutional mismatch repair deficiency (CMMRD). Current diagnostic tools are cumbersome inconsistent both childhood cancers determining germline MMRD. PATIENTS AND METHODS We developed analyzed a functional Low-pass Genomic Instability Characterization (LOGIC) assay to detect The performance LOGIC was compared that current...
To expand the clinical phenotype associated with STXBP1 gene mutations and to understand effect of in pathogenesis focal cortical dysplasia (FCD).Patients were identified various ways: as part a retrospective cohort study epileptic encephalopathy; through referrals individuals (10,619) developmental delay (DD) for chromosomal microarray; from collection 5,205 autism spectrum disorder (ASD) examined by whole-genome sequencing.Seven patients heterozygous de novo affecting coding region newly...
Hemimegalencephaly is a hamartomatous malformation of one hemisphere. Functional hemispherectomy, the definitive treatment, associated with significant morbidity and mortality in early infancy. Dysregulation mTOR pathway can result malformations cortical development, inhibitors effectively reduce seizures tuberous sclerosis complex. We report 6-day-old female hemimegalencephaly frequent despite 9 antiseizure medications. At 3 months age, while awaiting an inhibitor, rapamycin, was initiated...
The SickKids Cancer Sequencing (KiCS) Program, launched in 2016, evaluates the clinical utility of paired tumor/germline Next-Generation (NGS) pediatric oncology patients with hard-to-cure and rare cancers. In anticipation further widespread adoption NGS, we aimed to characterize experiences perspectives adolescents parents who have already undergone NGS evaluation, focusing on psychosocial impact personal utility.Parents cancer adolescent participated KiCS were invited participate...
Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer-predisposition disorder. Approximately 70% of individuals who fit the clinical definition LFS harbor a pathogenic germline variant in TP53 tumor suppressor gene. However, remaining 30% patients lack and even among carriers, approximately 20% remain cancer-free. Understanding variable cancer penetrance phenotypic variability critical to developing rational approaches accurate, early detection risk-reduction strategies. We leveraged...
Abstract Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals harbored variant found within exon 13 KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) in MSR1 (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs proband her mother were treated preoperative imatinib, which resulted severe intolerance. The clinical features GIST,...
Background Cancer predisposition syndromes (CPSs) are responsible for at least 10% of cancer diagnoses in children and adolescents, most which not clinically recognised prior to diagnosis. A variety clinical screening guidelines used healthcare settings help clinicians detect patients who have a higher likelihood having CPS. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) is an electronic health decision support tool that uses algorithms determine if child/adolescent...
Summary Despite advances in cancer therapeutics, early detection is often the best prognostic indicator for survival ( 1 ). People with Li-Fraumeni syndrome harbor a germline pathogenic variant tumor suppressor gene TP53 2 ) and face near 100% lifetime risk of developing wide spectrum of, multiple, cancers 3 mutation carriers routinely undergo intensive surveillance protocols which, although associated significantly improved survival, are burdensome to both patient health care system 4...
Abstract Between July of 2012 and December 2014, 39 patients were enrolled prospectively to investigate the prevalence glucose transporter 1 (GLUT1) deficiency in a ketogenic diet clinic. None them had GLUT1 deficiency. All seen same clinic within period reviewed retrospectively. A total 18 these 85 genetic diagnosis, including deficiency, pathogenic copy number variants, congenital disorder glycosylation, neuronal ceroid lipofuscinosis type II, mitochondrial disorders, tuberous sclerosis,...
ETV6-ABL1 gene fusion is a rare genetic rearrangement in variety of malignancies, including myeloproliferative neoplasms (MPN), acute lymphoblastic leukemia (ALL), and myeloid (AML). Here, we report the case 16-year-old male diagnosed with MPN, 7 months post-completion treatment for Burkitt leukaemia. RNA sequencing analysis confirmed presence an transcript, intact, in-frame ABL tyrosine–kinase domain. Of note, secondary ETV6-ABL1-rearranged neoplastic diseases have not been reported to...
<p>Figure S9 showing fragment length metrics in cfMeDIP libraries</p>
<p>Figure S2 showing panel-based TP53 copy number alterations</p>
<p>Supplemental Table 1 – Sample Descriptions</p>
<p>Figure S2 showing panel-based TP53 copy number alterations</p>
<p>Figure S12 showing longitudinal integration scores</p>