Leslie E. Oldfield
A5077898047- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Ovarian cancer diagnosis and treatment
- Genetic factors in colorectal cancer
- Cancer-related Molecular Pathways
- HIV Research and Treatment
- Genetics, Bioinformatics, and Biomedical Research
- Epigenetics and DNA Methylation
- Immunodeficiency and Autoimmune Disorders
- Genomic variations and chromosomal abnormalities
- BRCA gene mutations in cancer
- Endometrial and Cervical Cancer Treatments
- Genomics and Chromatin Dynamics
- Genomics and Rare Diseases
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Multiple and Secondary Primary Cancers
- Lung Cancer Treatments and Mutations
- Science, Research, and Medicine
- Sarcoma Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Animal Genetics and Reproduction
- Cancer-related molecular mechanisms research
- Colorectal Cancer Screening and Detection
- Chronic Lymphocytic Leukemia Research
Griffith University
2025
Princess Margaret Cancer Centre
2019-2024
University of Toronto
2017-2024
The University of Queensland
2024
University Health Network
2019-2024
Royal College of Surgeons in Ireland
2023
University of Liverpool
2023
McGill University
2023
Health Net
2023
Ontario Institute for Cancer Research
2017
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...
To evaluate the use of blood cell-free DNA (cfDNA) to identify emerging mechanisms resistance PARP inhibitors (PARPi) in high-grade serous ovarian cancer (HGSOC).
Abstract We report a case of Mismatch Repair Deficiency (MMRD) caused by germline homozygous EPCAM deletion leading to tissue-specific loss MSH2. Through the use patient-derived cells and organoid technologies, we performed stepwise in vitro differentiation colonic brain organoids from reprogrammed del iPSC derived patient fibroblasts. Differentiation epithelial-colonic exhibited continuous increased expression hypermethylation MSH2 promoter. This was associated with expression, mutational...
Background For women with ovarian cancer (OC), the optimal screening strategy to identify Lynch syndrome (LS) has not been determined. In current study, authors compared performance characteristics of various strategies combining mismatch repair (MMR) immunohistochemistry (IHC), microsatellite instability testing (MSI), and family history for detection LS. Methods Women nonserous and/or nonmucinous were recruited prospectively from 3 centers in Ontario, Canada. All underwent germline LS...
Von Hippel-Lindau disease (VHL) is an autosomal dominant, inherited syndrome with variants in the VHL gene causing predisposition to multi-organ benign and malignant neoplasms. A germline variant identified 95-100% of individuals a clinical diagnosis VHL. Here, we present case individual where peripheral blood DNA analysis did not detect variant. Sequencing four tumor tissues (ccRCC, pheochromocytoma, lung via sputum, liver) revealed c.593 T > C (p.Leu198Pro) at varying allele fractions...
Germline pathogenic TP53 variants predispose individuals to a high lifetime risk of developing multiple cancers and are the hallmark feature Li-Fraumeni syndrome (LFS). Our group has previously shown that LFS patients harbor shorter plasma cell-free DNA fragmentation; independent cancer status. To understand functional underpinning cfDNA fragmentation in LFS, we conducted fragmentomic analysis 199 samples from 82 mutation carriers 30 healthy TP53-wildtype controls. We find exhibit an...
Clinical testing for mismatch repair (MMR) deficiency often entails serial of tumor and constitutional DNA using multiple assays. To minimize cost specimen requirements MMR testing, we developed an integrated targeted sequencing protocol (termed MultiMMR) that tests promoter methylation, mutations, copy number alterations, neutral loss heterozygosity, microsatellite instability from a single aliquot DNA. Hybrid capture DNA-sequencing libraries constructed with methylated adapters was...
Despite recommendations for reflex immunohistochemistry (IHC) mismatch repair (MMR) proteins to identify Lynch syndrome (LS), the uptake of genetic assessment by those who meet referral criteria is low. The authors implemented a comprehensive navigation program increase testing LS in patients with endometrial cancer (EC) or nonserous/nonmucinous ovarian (OC).Participants newly diagnosed EC OC were prospectively recruited from 3 centers Ontario, Canada. Family history questionnaires used...
We explored health professionals' views on the utility of circulating tumor DNA (ctDNA) testing in hereditary cancer syndrome (HCS) management.A qualitative interpretive description study was conducted, using semi-structured interviews with professionals across Canada. Thematic analysis employing constant comparison used for analysis. 2 investigators coded each transcript. Differences were reconciled through discussion and codebook modified as new codes themes emerged from data.Thirty-five...
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...
Objectives For synchronous endometrial and ovarian cancers, most centers rely on mismatch repair testing of the cancer to identify Lynch syndrome, neglect tumor site completely. We examined immunohistochemistry microsatellite instability results from endometrium ovary assess discordance between sites tests. Methods 30 women with newly diagnosed were prospectively recruited three in Ontario, Canada. Both assessed for deficiency by test; test at each was examined. Cases discordant had tumors...
Whole-genome sequencing of primary breast tumors enabled the identification cancer driver genes and noncoding plexuses from somatic mutations. However, differentiating passenger events among genetic variants remains a challenge. Herein, we reveal cancer-driver cis-regulatory elements linked to transcription factors previously shown be involved in development luminal cancers by defining tumor-enriched catalogue approximately 100,000 unique 26 estrogen receptor (ER)+ progesterone (PR)+ tumors....
<h3>Objectives</h3> Abnormalities in mismatch repair have been described ovarian cancer, but few studies examined the causes of deficiency (MMRd). To address this, we completed targeted mutational and methylation sequencing on MMRd cancer cases. The objective this study was to explore molecular mechanism using our next generation panel. <h3>Methods</h3> Newly diagnosed non-serous/mucinous cancers (n=215) were prospectively recruited from three centers Ontario, Canada, between 2015 2018....
<p>Figure S9 showing fragment length metrics in cfMeDIP libraries</p>