Detection Of Somatic Mutations In Sporadic Epilepsies
Funder
National Health and Medical Research Council
Funding Amount
$1,256,166.00
Summary
Finding genetic causes of epilepsies is essential for refining treatments and genetic counseling. Genetic mutations may occur after fertilization (somatic mutations). These can be difficult to detect by routine genetic tests. We aim to identify somatic mutations by: very deep sequencing of blood to find low concentrations of mutations, analysing DNA from the cerebrospinal fluid, and analysing DNA obtained from the back of the nose which is closely related to brain tissue.
Somatic Retrotransposition Drives Neoplastic Mutagenesis In Glioblastoma Multiforme
Funder
National Health and Medical Research Council
Funding Amount
$667,342.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves in our genome. Previously thought to represent “junk DNA”, retrotransposons are increasingly found to play major roles in biology. In a recent landmark publication in Nature, we demonstrated that retrotransposons move in the healthy human brain. In the current study, we will use cutting-edge technologies to determine whether brain cancer can occur as a result. This will provide new perspectives of the genetic basis for cancer.
The Role Of Somatic Mutations In CCCTC-binding Factor (CTCF) Binding Sites In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$371,114.00
Summary
The three dimensional organisation of genomic DNA has been recognised to play a crucial role in maintaining the stability and function of human cells. In cancer this organisation is often perturbed as a result of mutations to proteins that govern this process. This project will examine how mutations in the DNA may potentially alter the three dimensional organisation of cancer genomes and will identify links between these mutations with cancer development and patient prognosis.
Consequences Of MYD88 Mutations Commonly Found In Human B Cell Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$442,583.00
Summary
MYD88 is one of the most recurrently mutated genes in B cell malignancies, such as diffuse-large B cell lymphoma and Waldenström macroglobulinemia. This project will characterise oncogenic MYD88 mutations by introducing the mutations into normal mouse B cells. It will examine how the mutations disrupt signalling pathways and B cell functions and how the mutations respond to new lymphoma drugs. We hope this project will provide information for lymphoma pathogenesis and rational drug selection.
Understanding Causes Of The Rising Incidence Of Thyroid Cancer – What Can Mutations In The BRAF Oncogene Tell Us About Causes And Diagnostic Pathways For Thyroid Cancer?
Funder
National Health and Medical Research Council
Funding Amount
$610,222.00
Summary
The occurrence of thyroid cancer has increased rapidly over the last 25 years but the cause is unknown. The increase may reflect ‘over-diagnosis’ of less harmful cancers or greater exposure to causes of this cancer. Evidence suggests that a gene mutation (BRAF) in thyroid cancers is important in understanding the drivers of the increase. This study will examine the increase in thyroid cancer by investigating causes and diagnostic pathways considering the presence or absence of BRAF mutations.
Immunoglobulin Germline Genes, BCR Repertoire Development And Disease Susceptibility. An Investigation Of Haplotypic Variation Between Individuals
Funder
National Health and Medical Research Council
Funding Amount
$519,828.00
Summary
The immune system is capable of making a repertoire of protective antibodies including literally tens of millions of different specificities. These are produced by permutations and combinations of a small set of ‘germline’ genes. This project will analyse how individual variations in the germline genes lead to individual differences in the repertoires of available antibodies, and will investigate whether or not such differences contribute to our susceptibility to infection and autoimmune disease ....The immune system is capable of making a repertoire of protective antibodies including literally tens of millions of different specificities. These are produced by permutations and combinations of a small set of ‘germline’ genes. This project will analyse how individual variations in the germline genes lead to individual differences in the repertoires of available antibodies, and will investigate whether or not such differences contribute to our susceptibility to infection and autoimmune diseases.Read moreRead less
Expanding Diagnostic Approaches For Lynch Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$1,269,355.00
Summary
Currently, there are ~1,000 families who have attended Family Cancer Clinics across Australia who have the hallmarks of having Lynch syndrome, a hereditary bowel cancer syndrome, but who have no gene defect identified, i.e. their cancer is unexplained. Clinicians are challenged by these “Lynch-like” patients as their family cancer risk is unknown. Our research has identified new gene defects in Lynch-like patients. Our aim is to optimise clinical testing approaches for Lynch-like patients.
PRECISION: Personalised Risk Evaluation In DCIS, International
Funder
National Health and Medical Research Council
Funding Amount
$1,392,930.00
Summary
Ductal carcinoma in situ (DCIS) of the breast is a common diagnosis with problematic clinical management. This study brings together an international consortium to identify and validate clinical biomarkers of recurrence.
Analysis Of Circulating Tumour DNA For Mutational Characterisation And Tracking Disease Progression In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$908,676.00
Summary
Multiple myeloma is cancer of plasma cells in the bone marrow and presents at multiple sites with dissimilar genetic information (GI) across these sites. Invasive biopsies of multiple sites are required to determine the GI. Cancer cells shed small amounts of DNA into the blood stream and this circulating DNA (ctDNA) contains GI from multiple cancer sites. This project will evaluate the utility of ctDNA to determine GI and to predict treatment response in MM patients.
The Landscape Of Cancer Genes And Associations With Prognosis In Breast Cancer Diagnosed In Premenopausal Women
Funder
National Health and Medical Research Council
Funding Amount
$700,512.00
Summary
Using state of the art technology, the purpose of this project is understand the implications of known cancer mutations in breast cancer diagnosed in premenopausal ER-positive breast cancer. Mutations are abnormalities in the DNA of genes that can provide a signal for uncontrolled growth, a hallmark of cancer. The unique aspect of this project is use of tissue samples from patients who were diagnosed with breast cancer at a young age. This information will help us develop new treatments.