The Mutagenic Influence Of 5-methylcytosine And Its Relevance For Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$844,462.00
Summary
Over time our cells accumulate damage to their DNA, which introduces mistakes in the genetic code. These mistakes can alter genes that regulate cell growth and survival and, in this way, they begin the process of turning a normal cell into a cancer. This research is investigating the cellular repair mechanisms that safeguard against DNA damage. Manipulating these repair mechanisms may offer a new way to treat cancer, by selectively inducing DNA damage within cancer cells.
This study will address the idea that cancer commonly involves a genetic pathway that is normally used by stem cells to proliferate in an undifferentiated state. We have evidence to indicate that this system is active in cancer cells and believe this could explain how cancer cells manage to divide rapidly in a primitive state. This project may bring a new perspective to the study of malignant transformation and has the potential to reveal multiple new targets for cancer therapy.
Identification Of Genes Responsible For Familial Predispositions To Haematological Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$713,944.00
Summary
A successful approach to the identification of cancer genes has been to study the 5-10% of cases that occur in families with an inherited predisposition to develop cancer. In contrast to solid tumors, few cancer-causing germ-line mutations have been identified for hematological cancers. We are using cutting edge technologies to identify blood cancer genes in a collection of both Australian and international families and comparing them to similar sporadic cancers.
Genomic Profiling For The Prevention Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
Bowel cancer is a major health issue but is also a preventable disease. Identifying who has a high risk of developing bowel cancer from someone who has a low risk is an important way to ensure preventative medical treatment is targeted to those who are at the highest risk and will ultimately save lives. I will utilise different genomic profiling approaches to identify risk factors for bowel cancer so that they can be used to identify high risk people in the population.
Germline Epimutations Of Tumour Suppressor Genes In Familial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$502,500.00
Summary
In the case of bowel cancer, studies of the pattern of disease in our community indicate that up to 20% of all bowel cancers has a inherited component . We now know the genetic abnormality in up to 4% of these cases. We have recently discovered a previously unrecognised cause of cancer. Individuals who are affected by this disease may have cancer in the bowel, as well as the breast and womb. In this condition the gene alphabet is correct but the genes are chemically modified. This change called ....In the case of bowel cancer, studies of the pattern of disease in our community indicate that up to 20% of all bowel cancers has a inherited component . We now know the genetic abnormality in up to 4% of these cases. We have recently discovered a previously unrecognised cause of cancer. Individuals who are affected by this disease may have cancer in the bowel, as well as the breast and womb. In this condition the gene alphabet is correct but the genes are chemically modified. This change called methylation means that certain genes are spelt incorrectly or not at all. To date we have found two individuals who have this problem. Our work has shown that these individuals have inherited a genetic change and potentially could pass this change on to their offspring. This grant application seeks to formally pursue this findng. We will study a group of people in whom the genetic cause for their cancer remains unknown. Blood samples from these individuals will be examined for methylation of their DNA. A successful project will lead to a full description of this new type of hereditary cancer, and thus serve as the basis for identifying and effectively managing people and families at risk of this disease. It is likely that identification of individuals who are 'at risk' of cancer will allow us to implement preventative screening strategies. We will also be able to provide reassurance to those family members who have not inherited the methylation abnormality.Read moreRead less
Epigenetic Predictors Of Outcome In Malignant Glioma
Funder
National Health and Medical Research Council
Funding Amount
$697,720.00
Summary
Human high grade gliomas (HGG) present as heterogeneous disease, primarily defined by the histologic appearance of the tumor cells.Glioblastoma multiforme (GBM) is the most common illness and continues to have a very poor prognosis, despite the use of multimodality therapy including surgery, radiation therapy and chemotherapy. We will use our existing biobank of specimens, clinical information and molecular investigation to identify factors that determine outcomes.
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.
Determining The Causes And Consequences Of Epigenetic Remodelling In Cancer And Disease
Funder
National Health and Medical Research Council
Funding Amount
$863,413.00
Summary
The study of epigenetics and its role in gene control is proving to be the next major contributor to our future understanding and improvement of health outcomes. Professor Clark and her team are on a quest to unravel the secrets of human epigenome to help reduce the burden of human disease. Their research will help contribute to the discovery of genetic and epigenetic aberrations in cancer and other complex diseases with the development of new diagnostic tests and potential new epigenetic-based ....The study of epigenetics and its role in gene control is proving to be the next major contributor to our future understanding and improvement of health outcomes. Professor Clark and her team are on a quest to unravel the secrets of human epigenome to help reduce the burden of human disease. Their research will help contribute to the discovery of genetic and epigenetic aberrations in cancer and other complex diseases with the development of new diagnostic tests and potential new epigenetic-based therapies.Read moreRead less
Circulating Tumour DNA As A Noninvasive Biomarker In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$1,299,114.00
Summary
The expanding repertoire of treatment options in melanoma is bringing into focus the need for improved ways to accurately monitor treatment responses and guide treatment decisions. Many cancers shed small amounts of DNA (ctDNA) into the bloodstream and changes in ctDNA levels have potential to be used as specific markers of response to cancer therapy. This project will evaluate if ctDNA can be used as a form of ‘liquid biopsy’ to guide treatment decisions in patients with melanoma.
Molecular Determinants Of Susceptibility And Progression In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$6,006,551.00
Summary
Breast cancer is heterogeneous, making management a challenge. High-grade cancers including the ‘basal’ type are aggressive, often found in young women and have a propensity for distant spread. They are also associated with a BRCA1 gene mutation. We will study mechanisms that predispose some women to develop breast cancer, the process that allows cancers to grow at distant sites such as the brain and lungs, and how DNA repair proteins are implicated. This will allow development of new diagnostic ....Breast cancer is heterogeneous, making management a challenge. High-grade cancers including the ‘basal’ type are aggressive, often found in young women and have a propensity for distant spread. They are also associated with a BRCA1 gene mutation. We will study mechanisms that predispose some women to develop breast cancer, the process that allows cancers to grow at distant sites such as the brain and lungs, and how DNA repair proteins are implicated. This will allow development of new diagnostic tools and treatments.Read moreRead less