Population Genetics And Functional Genomics Approaches To Improve Outcomes For Patients With Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$466,492.00
Summary
Colorectal cancer (CRC) is the third leading cause of cancer related death in Australia, and the 5-year survival rate for metastatic disease remains below 10%. Over the next 4 years, my translational research program will focus on improving patient outcomes in four ways: Discovery of inherited variants affecting CRC risk and progression, tumour molecular classification, discovery of markers for prognosis and drug response, and elucidation of the molecular mechanisms driving CRC development.
Translational Genomics And Combinatorial Drug Discovery To Improve Outcomes For Patients With Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Bowel cancer is a major public health burden in Australia. Over the next 5 years, A/Prof Sieber’s research will focus on understanding the molecular pathology of bowel cancer and how this determines the course of disease and response to therapy. Integrated genomic, functional and drug discovery studies will provide significant new insights into fundamental tumour biology and open up new avenues for diagnosis and treatment.
Identification Of Novel Colorectal Cancer Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$358,093.00
Summary
Colon cancer is one of the most common cancers, with around 1 million cases diagnosed annually. These cancers can be caused by a combination of lifestyle/environmental and genetic factors. Genetics cause ~30% of colon cancers, although the cause is unexplained in ~2/3 of these cases. The aim of this project is to discover new colon cancer genes by extensive gene sequencing of multi-case unexplained colon cancer families, and screening of additional cases and cancer-free individuals.
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.
Microparticles As Novel Biomarkers In Liver Cancer
Funder
National Health and Medical Research Council
Funding Amount
$85,833.00
Summary
No current highly sensitive or specific diagnostic and prognostic biomarker for hepatocellular carcinoma (HCC) exists. We will identify novel nucleic acid signatures in the circulation of patients with HCC through Next Generation Sequencing. Plasma microvesicles will be isolated and their contents analyzed to identify novel genetic biomarkers and fusion gene constructs specific for HCC. Resultant panel of novel biomarkers for HCC will be validated on the Australian STREP cohort of HCC patients.
Harnessing Endogenous L1-mediated Mutagenesis To Elucidate New Candidate Genes For Liver Cancer
Funder
National Health and Medical Research Council
Funding Amount
$632,656.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves in our genome. Previously thought to represent “junk DNA”, retrotransposons are increasingly recognised to play major roles in biology. In a recent publication in Cell, we found that retrotransposons were highly active in some types of liver cancer, mutating key genes required to block tumour formation. In the current study, we will determine in greater depth how, and how often, these genes are involved in other types of liver canc ....Retrotransposons are mobile genes that copy-and-paste themselves in our genome. Previously thought to represent “junk DNA”, retrotransposons are increasingly recognised to play major roles in biology. In a recent publication in Cell, we found that retrotransposons were highly active in some types of liver cancer, mutating key genes required to block tumour formation. In the current study, we will determine in greater depth how, and how often, these genes are involved in other types of liver cancer.Read moreRead less
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
New High-risk Variants For Colorectal Cancer: The Post-GWAS Era
Funder
National Health and Medical Research Council
Funding Amount
$710,105.00
Summary
Our aim is to discover new genes that greatly increase bowel cancer risk. If we can identify these carriers we may be able to prevent them getting cancer. By studying DNA related to bowel cancer, using a novel family design, we will identify families most likely to carry the new genes. We will focus genetic testing, using new techniques, to look for mutations in these prioritised families. Identified mutations will be tested in a 3,500 bowel cancer cases to see how important they are.
Development Of A Comprehensive Model For Colorectal Cancer Risk Prediction
Funder
National Health and Medical Research Council
Funding Amount
$317,012.00
Summary
Bowel cancer is the second most common cause of cancer death in Australia. While the average lifetime risk is 1 in 20, this is a great difference in individual risks. Screening and early detection can prevent 90% of bowel cancer deaths. We need to know who is at high-risk and therefore can be targeted for screening. In this project, I will develop the first tool that can predict precisely an individual’s personal risk of bowel cancer.
Incorporating Genomics Into Breast Cancer Management
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
This study will investigate use of genomic sequencing in advanced and early breast cancer. We will characterise genetic characteristics of patients who benefit from two different therapies in the metastatic setting. We will use circulating tumour DNA analysis to monitor for and genetically characterise minimal residual disease (MRD) in patients apparently cured by initial therapy. This will thus identify potential therapeutic targets for preventing MRD progressing to metastatic disease.