Nadia Traficante
A5000030462- Ovarian cancer diagnosis and treatment
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- DNA Repair Mechanisms
- Renal cell carcinoma treatment
- Proteoglycans and glycosaminoglycans research
- Cancer Mechanisms and Therapy
- Immune cells in cancer
- BRCA gene mutations in cancer
- Cancer-related Molecular Pathways
- Cancer Immunotherapy and Biomarkers
- Sarcoma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Fibroblast Growth Factor Research
- Bioinformatics and Genomic Networks
- Evolution and Genetic Dynamics
- Genomics and Chromatin Dynamics
- Genomics and Phylogenetic Studies
Peter MacCallum Cancer Centre
2014-2024
The University of Melbourne
2015-2024
Monash University
2023
Hudson Institute of Medical Research
2023
Cedars-Sinai Medical Center
2022
Westmead Institute for Medical Research
2018
Roche (Switzerland)
2018
AstraZeneca (Brazil)
2018
Royal Women's Hospital
2015
U-M Rogel Cancer Center
2008
The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage clinical and pathologic features.Microarray was done on 285 serous endometrioid tumors the ovary, peritoneum, fallopian tube. K-means clustering applied robust subtypes. Statistical analysis identified differentially expressed genes, pathways, ontologies. Laser capture microdissection, pathology review, immunohistochemistry validated array-based findings. Patient survival within...
A significant number of women with serous ovarian cancer are intrinsically refractory to platinum-based treatment. We analyzed somatic DNA copy variation and gene expression data identify key mechanisms associated primary resistance in advanced-stage cancers.Genome-wide was measured 118 tumors using high-resolution oligonucleotide microarrays. well-defined subset 85 then used relate The discovery-based approach complemented by quantitative-PCR analysis 12 candidate genes as independent...
Abstract Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and cancer patients. The 12 HGSOC patient-derived xenografts (PDX) the rucaparib was assessed, variable dose-dependent responses observed chemo-naive BRCA1/2 -mutated PDX, no PDX...
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...
The purpose of this study was to estimate precise age-specific tubo-ovarian carcinoma (TOC) and breast cancer (BC) risks for carriers pathogenic variants in RAD51C RAD51D.
In high-grade serous ovarian carcinoma (HGSC), deleterious mutations in DNA repair gene RAD51C are established drivers of defective homologous recombination and emerging biomarkers PARP inhibitor (PARPi) sensitivity. promoter methylation (meRAD51C) is detected at similar frequencies to mutations, yet its effects on PARPi responses remain unresolved.In this study, three HGSC patient-derived xenograft (PDX) models with most or all examined CpG sites the show PARPi. Both complete heterogeneous...
The Drosophila SINA (seven in absentia) protein and its mammalian orthologs (Siah, seven absentia homolog) are RING domain proteins that function E3 ubiquitin ligase complexes facilitate ubiquitination degradation of a wide range cellular proteins, including β-catenin. Despite these diverse targets, the means by which SINA/Siah recognize substrates or binding has remained unknown. Here we identify peptide motif (RPVAxVxPxxR) mediates interaction Siah with partners. Sequence alignment...
Abstract Approximately, 10% to 15% of serous ovarian tumors fall into the category designated as low malignant potential (LMP). Like their invasive counterparts, LMP may be associated with extraovarian disease, for example, in peritoneal cavity and regional lymph nodes. However, unlike typical carcinomas, patients generally have a favorable prognosis. The mutational profile also differs markedly from that seen most carcinomas. Typically, are KRAS BRAF mutations. Interrogation expression...
Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and estradiol (E 2 ) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 cases 37 925 controls report the first genome wide-significant association between a SNP (rs727479 intron 2, P =4.8×10 −11 ). rs727479 was also among those most strongly circulating E concentrations 2767 post-menopausal ( =7.4×10 −8 The observed odds ratio per A-allele (1.15, CI=1.11–1.21) is...
Mucinous ovarian carcinoma (MOC) is an uncommon cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent advanced disease are associated extremely poor survival. There no current guidelines specifically for the systemic management of MOC. We analyzed data from a large cohort women MOC evaluate potential clinical utility range agents.We gene copy number (n =...
Abstract Purpose: Gene expression–based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation clinical utility has been hindered by nonstandardized methods, which are not applicable in a setting. We sought to generate grade minimal gene set assay classification individual tumor specimens into HGSOC and confirm previously reported subtype-associated...
PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade (LGSOC)). We aimed to characterise expression as biomarker epithelial large population-based study.
The mammalian Siah genes encode highly conserved proteins containing a RING domain. As components of E3 ubiquitin ligase complexes, facilitate the ubiquitination and degradation diverse protein partners including β-catenin, N-CoR, DCC. We used gene targeting in mice to analyze function Siah1a during development reveal novel roles growth, viability, fertility. Mutant animals have normal weights at term but are postnatally growth retarded, despite levels pituitary hormone. Embryonic...
Abstract We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning broad spectrum purity. identified patients with longer progression-free survival had increased immune-related signatures validated proteins correlating tumor-infiltrating lymphocytes in 65 tumors an independent cohort HGSOC patients, as well overall additional 126 patient cohort. that homologous...
Purpose The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk suggesting that other exist. aim this study was to evaluate contribution rare deleterious germline variants in a set candidate genes. Methods We sequenced coding region 54 6385 invasive EOC cases and 6115 controls broad European ancestry. Genes with an increased frequency putative versus were further examined independent 14 135 28 655 from Ovarian Cancer Association...
Abstract Purpose: Although ovarian clear cell carcinomas (OCCC) are commonly resistant to platinum-based chemotherapy, good clinical outcomes observed in a subset of patients. The explanation for this is unknown but may be due misclassification high-grade serous cancer (HGSOC) as OCCC or mixed histology. Experimental Design: To discover potential biomarkers survival benefit following we ascertained cohort 68 Japanese and Australian patients whom progression-free (PFS) overall (OS) could...
Abstract The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells following chemotherapy is only partially understood. To understand the selection factors driving heterogeneity before and through adaptation to treatment, we profile single-cell RNA-sequencing (scRNA-seq) transcriptomes HGSOC tumors collected longitudinally during therapy. We analyze scRNA-seq data from two independent patient cohorts reveal that driven by three archetypal phenotypes, defined as oncogenic...
Abstract Our objective was to test whether p53 expression status is associated with survival for women diagnosed the most common ovarian carcinoma histotypes (high‐grade serous [HGSC], endometrioid [EC], and clear cell [CCC]) using a large multi‐institutional cohort from Ovarian Tumor Tissue Analysis (OTTA) consortium. assessed on 6,678 cases represented tissue microarrays 25 participating OTTA study sites previously validated immunohistochemical (IHC) assay as surrogate presence functional...