Genetic And Epigenetic Biomarkers In High Risk Colorectal Cancer: Predicting Risk Of Recurrence
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
The main aim of this project is to define the prognostic and predictive significance of specific genetic events in patients with high risk (stage III) colorectal cancer. We attempt to explore the differences between primary tumours from patients with and without recurrence at three years. Data from the project will then be used to define a limited set of biomarkers which will aid in clinical decisions regarding the need for adjuvant chemotherapy after surgery for high risk colorectal cancer.
I am a molecular biologist and my research is focussed on the importance of epigenetics in early development and disease, especially in cancer. My research to date has resulted in many ground-breaking discoveries relating to DNA methylation patterns, that
Epigenetic Silencing Of Large Chromosomal Regions In Prostate Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$745,356.00
Summary
Epigenetics is a term that desribes modification of gene expression without a change to the DNA sequence through processes that involve chemical change to the DNA such as methylation. In this grant we will further characterise and understand the mechanism involved in long range epigenetic silencing and determine its prevalence in prostate cancer. This study will provide potential novel targets for prostate cancer detection, prognosis and therapy.
DNA methylation is a mechanism used by many organisms, including humans, to keep certain regions of DNA inactive, i.e. in a state where they will not be read. Errors in this process may result in inappropriate inactivation of a gene, termed epimutation; this may occur even when no DNA sequence changes (i.e. mutations) are present. Some individuals are born with high levels of an epimutation that predisposes them to developing multiple cancers. Little is known about whether low levels of epimutat ....DNA methylation is a mechanism used by many organisms, including humans, to keep certain regions of DNA inactive, i.e. in a state where they will not be read. Errors in this process may result in inappropriate inactivation of a gene, termed epimutation; this may occur even when no DNA sequence changes (i.e. mutations) are present. Some individuals are born with high levels of an epimutation that predisposes them to developing multiple cancers. Little is known about whether low levels of epimutations (only a portion of the body's cells affected) are important in development of sporadic (common) cancer. The aim of this project is to determine the levels of epimutations in the normal tissues of healthy individuals, and compare these with the levels in normal tissues of people who have had certain types of cancers. In doing this we hope to find out if low level epimutations contribute to the risk of developing sporadic cancer.Read moreRead less
The recent cloning of the breast cancer predisposition gene, BRCA1 had an unexpected consequence. Whereas mutations were found in affected individuals from families showing a predisposition to breast and ovarian cancer, mutations were not identified in breast cancers from individuals with no family history. We have identified a type of change called an epigenetic change affecting BRCA1 in breast and ovarian cancers. Epigenetic changes are mechanisms which act at a gene without causing mutations ....The recent cloning of the breast cancer predisposition gene, BRCA1 had an unexpected consequence. Whereas mutations were found in affected individuals from families showing a predisposition to breast and ovarian cancer, mutations were not identified in breast cancers from individuals with no family history. We have identified a type of change called an epigenetic change affecting BRCA1 in breast and ovarian cancers. Epigenetic changes are mechanisms which act at a gene without causing mutations but nevertheless have the stability of genetic change. We plan to examine breast tumours for further epigenetic changes. This project has important implications for our understanding of the development of breast cancer. This new understanding may in turn suggest new strategies for the treatment of breast cancer.Read moreRead less
Further Characterisation Of The Role Of HSSB1 In DNA Repair And Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$85,526.00
Summary
To date, all breast cancer predisposition genes identified play an important role in the DNA damage repair pathway. We have characterised a new protein designated as hSSB1, which plays a crucial role in the maintenance of genomic stability by protecting us from DNA damage. Significantly, evidence strongly suggests an interaction of hSSB1 with the breast cancer susceptibility protein BRCA2. This project will investigate the role of hSSB1 in breast cancer predisposition and DNA damage repair.