Clinical Classification Of Regulatory Variants In Breast Cancer Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$536,966.00
Summary
Variations in our genes can confer a risk of diseases including breast cancer. Determining the clinical significance of these variations is a major and increasing challenge for genetic counselors and clinicians. This project will evaluate the clinical significance of variants in the control regions of breast cancer susceptibility genes. This research will inform the development of guidelines for interpreting such variants in a clinical setting.
Cancer is a genetic disease – it occurs because of genetic changes in the body that change how a cell grows, and because it occurs more often in people who have an inherited predisposition to cancer. My aim is to uncover more of the genetic events that give rise to cancer, particularly of the breast, ovary and stomach, so that we can identify people at high risk, and advice them accordingly, and also so that we can devise better treatments directed at particular genetic alterations.
High-Throughout Identification And Targeting Of New Breast Cancer Genes.
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Recent studies have identified DNA sequence variations within the human genome that are associated with an increased risk or can influence the outcome of breast cancer. This research program will identify the key genes affecting cancer development and assess their contribution to cancer growth. I will then use this knowledge to assess their suitability for drug development. Understanding how our DNA contributes to breast cancer will provide new avenues for prevention or treatment.
Lung cancer is a leading cause of cancer death globally. Symptoms may not develop until disease is advanced, so it is often incurable at diagnosis. Scientific developments have greatly improved our ability to test for the changes in DNA structure and function responsible for this deadly disease and its progression. This study examines whole lung cancer genomes then uses these findings to develop safer methods for detection based on changes in DNA sequence.
Understanding The Genetic Basis Of Breast Cancer: Translation To Primary And Secondary Prevention
Funder
National Health and Medical Research Council
Funding Amount
$2,731,372.00
Summary
We have identified >200 regions of the genome that contain variants that increase breast cancer risk. I will now focus on the main challenges i.e. to a) find the remaining genetic risk factors that will collectively explain all of the genetic risk, b) understand how these work, in particular which genes they influence and c) apply this knowledge to find and develop new drugs. Importantly, such drugs could be used not only to treat breast cancer, but also to prevent it in high-risk women.
Genomic Approaches To Understanding Tasmanian Devil Facial Tumor Disease
Funder
National Health and Medical Research Council
Funding Amount
$210,855.00
Summary
Devil facial tumor disease (DFTD) is an emerging infectious disease affecting Tasmanian devils. DFTD is a transmissible cancer, and results in the growth of large tumors usually on the face and mouth of affected animals. DFTD has led to the collapse of the Tasmanian devil population, and there is concern that the disease will drive devils to extinction in the wild within the next 20 years. I propose to use new genome sequencing technologies to discover genes responsible for DFTD.
Spatial And Temporal Aspects Of Epigenetic Remodelling In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$626,707.00
Summary
Epigenetic deregulation occurs commonly in cancer, and can affect not only single genes but can encompass large chromosomal domains, leading to altered expression of oncogenes and tumour suppressor genes, and genomic instability. We will investigate the role of epigenetic remodeling, how spacial reorganisation of the genome, nuclear architecture, chromatin looping and replication timing may affect long range epigenetic deregulation, and ultimately contribute to cancer formation and progression.
Genome-wide Study Of Loss Of Heterozygosity Using High Density SNP Arrays To Identify Breast Cancer Predisposition Genes
Funder
National Health and Medical Research Council
Funding Amount
$542,599.00
Summary
The genes responsible for the majority of breast cancer families remain unknown. The genes BRCA1 and BRCA2 can prevent the development of cancer and represent a class of gene known collectively as 'tumor suppressors'. One of the hallmarks of these genes is that they show loss of the normal copy of the gene in tumors that arise in individual carrying one inherited, mutated copy. The broad aim of this proposal is to exploit this phenomenon to identify novel tumor suppressor genes that predispose t ....The genes responsible for the majority of breast cancer families remain unknown. The genes BRCA1 and BRCA2 can prevent the development of cancer and represent a class of gene known collectively as 'tumor suppressors'. One of the hallmarks of these genes is that they show loss of the normal copy of the gene in tumors that arise in individual carrying one inherited, mutated copy. The broad aim of this proposal is to exploit this phenomenon to identify novel tumor suppressor genes that predispose to familial breast cancer. This will be done by analyzing tumors from families that do not have either BRCA1 or BRCA2 mutations. Candidate tumor suppressor genes will be identified when tumors from different individuals in the same family all appear to have lost one copy of a gene, and retained the same copy, in a particular chromosomal region. We study tumours from non-BRCA1-2 breast cancer families using genetic techniques that are able to rapidly and accurately identify which parts of the chromosomes have been lost. Families will be identified in which all the tumors have lost exactly the same part of the chromosome. Next, we will exploit the fact that the entire sequence of the human genome is completed to find out which genes are located within the candidate region. We will then apply other technologies to identify which of these 'candidate genes' is actually responsible for the cancer in that family. Following this, we will investigate other families with a history of breast cancer to see how many can be accounted for by mutations in this gene. It is possible that we may identify more than on breast cancer gene using this powerful approach. Identification of new breast cancer predisposition genes would have major clinical relevance to the families directly affected, and much wider relevance if the same gene (or pathway) is later found to be involved in the causes of other familial or sporadic breast cancers.Read moreRead less
High Resolution Genome-wide SNP Analysis Of Genetic Alterations In Early Ovarian Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$587,055.00
Summary
Ovarian cancer is the 5th leading cause of cancer death in women. For such a significant disease, remarkably little is know about its origins and this has limited progress in developing more effective diagnostic markers. We will undertake cutting edge genome-wide analysis of pre-invasive ovarian tumours to identify genetic markers relevant to malignancy. This work will significantly expand our understanding of how ovarian cancers develops.