Michael S. Anglesio
A5026586433- Ovarian cancer diagnosis and treatment
- Endometrial and Cervical Cancer Treatments
- Cancer-related molecular mechanisms research
- Cancer Genomics and Diagnostics
- Endometriosis Research and Treatment
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- Reproductive System and Pregnancy
- Cancer Mechanisms and Therapy
- Ferroptosis and cancer prognosis
- Reproductive Biology and Fertility
- Kruppel-like factors research
- Chromatin Remodeling and Cancer
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Renal cell carcinoma treatment
- CRISPR and Genetic Engineering
- Uterine Myomas and Treatments
- MicroRNA in disease regulation
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- RNA Research and Splicing
- Cancer, Lipids, and Metabolism
University of British Columbia
2016-2025
BC Cancer Agency
2010-2024
Vancouver General Hospital
2011-2024
Women's Health Research Institute
2023-2024
Peter MacCallum Cancer Centre
2008-2023
Cancer Council NSW
2023
University of British Columbia Hospital
2021-2023
University of Northern British Columbia
2021
MUSC Hollings Cancer Center
2021
Medical University of South Carolina
2021
Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described.We sequenced whole transcriptomes of 18 ovarian 1 carcinoma cell line found somatic mutations ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) 6 samples. encodes BAF250a, a key component SWI–SNF chromatin remodeling complex. We an additional 210 second measured BAF250a expression by means immunohistochemical analysis 455...
BACKGROUND Classification of endometrial carcinomas (ECs) by morphologic features is irreproducible and imperfectly reflects tumor biology. The authors developed the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), a molecular classification system based on Genome Atlas genomic subgroups, sought to confirm both feasibility prognostic ability in new, large cohort ECs. METHODS Immunohistochemistry (IHC) presence or absence mismatch repair (MMR) proteins (to identify MMR...
Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% reproductive-age women can cause pelvic pain infertility. Endometriotic lesions are considered to be benign inflammatory but have cancerlike features such local invasion resistance apoptosis.
Germline truncating mutations in DICER1, an endoribonuclease the RNase III family that is essential for processing microRNAs, have been observed families with pleuropulmonary blastoma-family tumor and dysplasia syndrome. Mutation carriers are at risk nonepithelial ovarian tumors, notably sex cord-stromal tumors.We sequenced whole transcriptomes or exomes of 14 tumors noted closely clustered region DICER1 encoding IIIb domain four samples. We then this additional certain other queried effect...
High-grade serous ovarian cancer (HGSC) is characterized by poor outcome, often attributed to the emergence of treatment-resistant subclones. We sought measure degree genomic diversity within primary, untreated HGSCs examine natural state tumour evolution prior therapy. performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on 31 spatially temporally separated HGSC specimens (six patients), including masses, distant metastases...
Ovarian clear cell adenocarcinoma (OCCA) is an uncommon histotype that generally refractory to platinum-based chemotherapy. We analyze here the most comprehensive gene expression and copy number data sets, date, identify potential therapeutic targets of OCCA.Gene DNA were carried out using primary human OCCA tumor samples, findings confirmed by immunohistochemistry on tissue microarrays. Circulating interleukin (IL) 6 levels measured in serum from patients with or high-grade serous cancers...
OVARIAN CARCINOMAS CONSIST OF AT LEAST FIVE DISTINCT DISEASES: high-grade serous, low-grade clear cell, endometrioid, and mucinous. Biomarker molecular characterization may represent a more biologically relevant basis for grouping treating this family of tumors, rather than site origin. Molecular characteristics have become the new standard clinical pathology, however development tailored type-specific therapies is hampered by failure basic research to recognize that model systems used study...
Many women with ovarian endometrioid carcinoma present concurrent endometrial carcinoma. Organ-confined and low-grade synchronous tumors (SEOs) clinically behave as independent primary rather than a single advanced-stage We used 18 SEOs to investigate the ancestral relationship between components. Based on both targeted exome sequencing, 17 of patient cases simultaneous cancer endometrium ovary from our series showed evidence clonal relationship, ie, tumor metastasis. Eleven fulfilled...
Abstract Mucinous ovarian carcinoma (MOC) is a unique subtype of cancer with an uncertain etiology, including whether it genuinely arises at the ovary or metastatic disease from other organs. In addition, molecular drivers invasive progression, high-grade and are poorly defined. We perform genetic analysis MOC across all histological grades, benign borderline mucinous tumors, compare these to tumors potential extra-ovarian sites origin. Here we show that distinct supports progressive model...
YB-1 is a broad-specificity RNA-binding protein that involved in regulation of mRNA transcription, splicing, translation, and stability. In both germinal somatic cells, related proteins are major components translationally inactive messenger ribonucleoprotein particles (mRNPs) mainly responsible for storage mRNAs silent state. However, mechanisms regulating the repressor activity not well understood. Here we demonstrate association with capped 5′ terminus regulated via phosphorylation by...
Molecular subtypes of serous ovarian cancer have been recently described. Using data from independent datasets including over 900 primary tumour samples, we show that deregulation the Let-7 pathway is specifically associated with C5 molecular subtype cancer. DNA copy number and gene expression HMGA2, alleles Let-7, LIN28, LIN28B, MYC, MYCN, DICER1, RNASEN were measured using microarray quantitative reverse transcriptase PCR. Immunohistochemistry was performed on 127 samples tissue...
Abstract Mucinous ovarian carcinomas ( MCs ) typically do not respond to current conventional therapy. We have previously demonstrated amplification of HER2 in 6 33 (18.2%) mucinous and presented anecdotal evidence response with ‐targeted treatment a small series women recurrent ‐amplified +) MC . Here, we explore KRAS mutation status an independent cohort 189 199 borderline tumours MBOTs their association clinicopathological features. was assessed by immunohistochemistry IHC ), FISH , CISH...
Low grade serous ovarian tumours are a rare and under-characterised histological subtype of epithelial tumours, with little known the molecular drivers facilitators tumorigenesis beyond classic oncogenic RAS/RAF mutations. With move towards targeted therapies due to chemoresistant nature this subtype, it is pertinent more fully characterise genetic events driving tumour type, some which may influence response therapy and/or development drug resistance. We performed genome-wide...
Abstract Endometriosis is a significant risk factor for clear cell and endometrioid ovarian cancers often found contiguous with these cancers. Using whole‐genome shotgun sequencing of seven carcinomas ( CCC ) targeted in synchronous endometriosis, we have investigated how this carcinoma may evolve from endometriosis. In every case observed multiple tumour‐associated somatic mutations at least one concurrent endometriotic lesion. ARID1A PIK3CA appeared consistently endometriosis when present...
Abstract Our group recently described recurrent somatic mutations of the miRNA processing gene DICER1 in non‐epithelial ovarian cancer. Mutations appeared to be clustered around each four critical metal‐binding residues RNase IIIB domain . This is responsible for cleavage 3′ end 5p strand a pre‐ mRNA hairpin. To investigate effects these cancer‐associated 'hotspot' mutations, we engineered mouse ‐deficient ES cells express wild‐type and an allelic series mutant variants. Global profiles from...
Mucinous ovarian tumors represent a distinct histotype of epithelial cancer. The rarest (2-4 % carcinomas) the five major histotypes, their genomic landscape remains poorly described. We undertook hotspot sequencing 50 genes commonly mutated in human cancer across 69 mucinous tumors. Our goals were to establish overall frequency cancer-hotspot mutations large cohort, especially those previously thought be “RAS-pathway alteration negative”, using highly-sensitive next-generation as well...
Abstract PPP2R1A mutations have recently been described in 3/42 (7%) of clear cell carcinomas the ovary. encodes α‐isoform scaffolding subunit serine/threonine protein phosphatase 2A (PP2A) holoenzyme. This putative tumour suppressor complex is involved growth and survival pathways. Through targeted sequencing , we identified somatic missense 40.8% (20/49) high‐grade serous endometrial tumours, 5.0% (3/60) endometrioid carcinomas. Mutations were also ovarian tumours at lower frequencies:...
Abstract Purpose: Tumors with high mutation load are thought to engender stronger immune responses, which in turn promote prolonged patient survival. To investigate this, we assessed tumor-infiltrating lymphocytes (TILs) and immunosuppressive factors across the 4 molecular subtypes of endometrial cancer, have characteristic rates ranging from low ultra-high. Experimental Design: A total 460 cancers were stratified by ProMisE (Proactive Molecular Risk Classifier Endometrial cancer) into...
The advent of next generation sequencing has vastly improved the resolution mutation detection, thereby both increasing analysis cancer tissues and shining light on existence somatic driver mutations in normal tissues, even absence cancer. Studies have described skin, blood, peritoneal washings, esophageal epithelium. Such findings prompt speculation whether such exist other as eutopic endometrium particular, due to highly regenerative nature recent observation recurrent deep infiltrating...