A5031492399- BRCA gene mutations in cancer
- Genomics and Rare Diseases
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Global Cancer Incidence and Screening
- Ovarian cancer diagnosis and treatment
- DNA Repair Mechanisms
- Ethics in Clinical Research
- Genomic variations and chromosomal abnormalities
- Colorectal Cancer Screening and Detection
- Prenatal Screening and Diagnostics
- Health Systems, Economic Evaluations, Quality of Life
- Adrenal and Paraganglionic Tumors
- Cardiac electrophysiology and arrhythmias
- Cancer Risks and Factors
- Cancer, Hypoxia, and Metabolism
- Cardiovascular Effects of Exercise
- Cancer-related Molecular Pathways
- Colorectal Cancer Treatments and Studies
- Menopause: Health Impacts and Treatments
- Cardiomyopathy and Myosin Studies
- Acute Myeloid Leukemia Research
- Nutrition, Genetics, and Disease
- Cancer and Skin Lesions
- Biomedical Ethics and Regulation
Peter MacCallum Cancer Centre
2016-2025
The Royal Melbourne Hospital
2016-2025
The University of Melbourne
2014-2024
Victorian Comprehensive Cancer Centre
2018-2021
Hunter Medical Research Institute
2016
Campbell University
2016
King's College London
2011
UNSW Sydney
2009-2010
Monash Medical Centre
2010
Centre for Life
2009
Gene panel sequencing is revolutionizing germline risk assessment for hereditary breast cancer. Despite scant evidence supporting the role of many these genes in cancer predisposition, results are often reported to families as definitive explanation their family history. We assessed frequency mutations 18 included panels among index cases from with and matched population controls.Cases (n = 2,000) were predominantly cancer-affected women referred specialized Familial Cancer Centers on basis...
Despite intensive efforts using linkage and candidate gene approaches, the genetic etiology for majority of families with a multi-generational breast cancer predisposition is unknown. In this study, we used whole-exome sequencing thirty-three individuals from 15 to identify potential predisposing genes. Our analysis identified heterozygous, deleterious mutations in DNA repair genes FANCC BLM, which are responsible autosomal recessive disorders Fanconi Anemia Bloom syndrome. total, screening...
Abstract Mendelian-like inheritance of germline DNA methylation in cancer susceptibility genes has been previously reported. We aimed to scan the genome for heritable marks associated with breast by studying 25 Australian multiple-case families. Here we report genome-wide measured 210 peripheral blood samples provided family members using Infinium HumanMethylation450. develop and apply a new statistical method identify based on complex segregation analysis. estimate carrier probabilities...
To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease.We performed clinically accredited singleton ES a prospectively ascertained cohort 204 assessed multidisciplinary renal genetics clinics at four tertiary hospitals Melbourne, Australia.ES identified molecular diagnosis 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age presentation was independently associated an (p < 0.001). Of those...
Abstract Phaeochromocytomas ( PCCs ) and paragangliomas PGLs are rare neural crest‐derived tumours originating from adrenal chromaffin cells or extra‐adrenal sympathetic parasympathetic tissues. More than a third of PCC / PGL cases associated with heritable syndromes involving 13 more known genes. These genes have been broadly partitioned into two groups based on pseudo‐hypoxic receptor tyrosine kinase RTK signalling pathways. Many these can also become somatically mutated, although up to...
Diagnostic genomic sequencing is the emerging standard of care in nephrology. There a growing need to scale up implementation diagnostics nationally improve patient outcomes.
There is strong evidence that overtly inactivating mutations in RAD51C predispose to hereditary breast and ovarian cancer but the prevalence of such mutations, whether they are associated with a particular clinical phenotype, remains unclear. Resolving these questions has important implications for implementation into routine genetic testing. Consequently, we have performed large mutation screen families, first study unselected patients diagnosed cancer. Our data confirm consistent low...
Until recently, determining penetrance required large observational cohort studies. Data from the Exome Aggregate Consortium (ExAC) allows a Bayesian approach to calculate penetrance, in that population frequencies of pathogenic germline variants should be inversely proportional their for disease. We tested this hypothesis using data two cohorts succinate dehydrogenase subunits A, B and C (SDHA-C) genetic associated with hereditary pheochromocytoma/paraganglioma (PC/PGL).Two were 575...
To assess the relative cost-effectiveness of cascade genetic testing in asymptomatic relatives patients with dilated cardiomyopathy (DCM) compared periodical clinical surveillance.A decision-analytic model, combining a decision tree and Markov was used to determine lifetime costs quality-adjusted life years (QALYs) for two strategies. Deterministic probabilistic sensitivity analyses were undertaken robustness findings explore uncertainty.The incremental cost per additional QALY prior...
Decision support tools for the assessment and management of breast cancer risk may improve uptake prevention strategies. End-user input in design such is critical to increase clinical use. Before developing a computerized tool, we examined clinicians' practice future needs. Twelve surgeons, 12 primary care physicians 5 nurses participated 4 focus groups. These were recorded, coded, analyzed identify key themes. Participants identified difficulties assessing risk, including lack available...
<h3>Objectives</h3> To comprehensively ascertain the extent and severity of clinical features in affected individuals from 2 large families with proven heterozygous mutations the<i>CYLD</i>locus to correlate these findings 3 appendageal tumor predisposition syndromes (familial cylindromatosis, Brooke-Spiegler syndrome, multiple familial trichoepitheliomas) known be associated such germline mutations. <h3>Design</h3> Interfamilial intrafamilial observational study. <h3>Setting</h3> Tertiary...
Purpose/Objectives: To identify women's information and communication preferences about treatment-focused genetic testing (TFGT) in the ovarian cancer context.
DNA mismatch repair immunohistochemistry on tumor tissue is a simple, readily available, and cost-effective method of identifying patients with Lynch syndrome in the postoperative setting. The aim study was to assess whether status colorectal cancer can be confirmed by preoperative biopsy.Germline positive were identified from prospectively collected Familial Cancer Clinic database. Preoperative biopsy specimens obtained source pathology provider generate cohort matched specimens. sectioned...
Mutations in RAD51D have been associated with an increased risk of hereditary ovarian cancer and although they observed the context breast families, association is unclear. The aim this current study was to validate reported assess for cancer. We screened mutations BRCA1/2 mutation-negative index cases from 1,060 familial and/or families (including 741 affected by only) 245 unselected cases. Exons containing novel non-synonymous variants were 466 controls. Two overtly deleterious identified...
PALB2 is emerging as a high-penetrance breast cancer predisposition gene in the order of BRCA1 and BRCA2. However, large studies that have evaluated full rather than just most common variants both cases controls are required before all truncating can be included familial variant testing. In this study we analyse almost 2000 sourced from individuals referred to clinics, thus representing typical presenting clinical practice. These were compared similar number population-based cancer-free...
We aimed to develop a user-centered, web-based, decision support tool for breast cancer risk assessment and personalized management. Using novel model choice algorithm, iPrevent® selects one of two validated estimation models (IBIS or BOADICEA), based on factor data entered by the user. Resulting estimates are presented in simple language graphic formats easy comprehension. then presents risk-adapted, evidence-based, guideline-endorsed management options. Development was an iterative process...
Unexplained sudden cardiac death (SCD) may be attributable to cardiogenetic disease. Presence or absence of autopsy anomalies detected following premature direct appropriate clinical evaluation at-risk relatives towards inherited cardiomyopathies primary arrhythmia syndromes, respectively. We investigated the relevance non-diagnostic pathological abnormalities indeterminate causality (uncertain) such as myocardial hypertrophy, fibrosis, inflammatory infiltrates SCD.At-risk unexplained SCD...
Abstract The breast cancer predisposition gene, BRCA2 , has a large number of genetic variants unknown effect. variant rs11571833, an A > T transversion in the final exon gene that leads to creation stop codon 93 amino acids early (K3326*), is reported as neutral polymorphism but there some evidence suggest association with increased risk cancer. We assessed whether this was enriched cohort cases ascertained through familial clinics compared population-based non-cancer controls using...
Abstract Context: Pheochromocytomas and paragangliomas (PPGLs) are heritable neoplasms that can be classified into gene-expression subtypes corresponding to their underlying specific genetic drivers. Objective: This study aimed develop a diagnostic research tool (Pheo-type) capable of classifying PPGL tumors could used guide interpret testing, determine surveillance programs, aid in elucidation biology. Design: A compendium published microarray data representing 205 was for the selection...
Background Familial dilated cardiomyopathy (DCM) is characterized by marked variability in phenotypic penetrance. The extent to which this determined patient‐specific environmental factors unknown. Methods and Results A retrospective longitudinal cohort study was performed families with DCM‐causing genetic variants. Environmental were classified into 2 subsets based on evidence for a causal link depressed myocardial contractility, termed (1) DCM‐promoting (2) heart failure comorbidities....