There is a need to improve early detection, monitoring of relapse, and treatments for melanoma, to increase long-term survival. My research vision is to use innovative and cutting edge approaches to conduct a range of complementary studies under three broad but inter-related themes: Theme 1 – Genetic predisposition to melanoma in the general population; Theme 2 – Genetic predisposition to melanoma in high-density families; Theme 3 – Somatic aberrations underlying melanoma development.
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.
We have entered an era where it is now possible to sequence an individual's genetic blueprint. In the case of cancer this can be used to determine the genetic damage that has occurred in cancer cells. This fellowship seeks to carry out large scale sequencing of cancer patient and map out the genetic damage that is common to get a handle on what drives the disease. It will also investigate how personalized mutation detection might improve cancer treatment selection for individual patients.
A Worldwide Study Of Cancer Risk For Lynch Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$710,761.00
Summary
People with the genetic Lynch syndrome are more likely to get cancer but we cannot accurately predict who will get cancer and when. Doctors need this information to improve cancer prevention. Large collaborative studies are needed for this research. We have agreement from the 115 researchers to combine, into a single resource, 8,863 family trees of Lynch syndrome. We will analyse this data to determine the risk of cancer and whether it differs by sex, age, or nationality.
Melanoma Mutation Profiling For Personalised Treatment
Funder
National Health and Medical Research Council
Funding Amount
$571,191.00
Summary
Melanoma is an aggressive skin cancer, and the leading cause of skin cancer related deaths. Disease spread is difficult to detect and extremely difficult to cure. This bleak clinical outcome is changing with the development of personalised therapies which include small molecule inhibitors to treat metastatic melanoma. Here we seek to identify the spectrum of mutations in patient tumours and circulating tumour cells for advanced personalised treatment.
Identification And Characterisation Of Novel FLT3-ITD Co-operating Mutations
Funder
National Health and Medical Research Council
Funding Amount
$659,245.00
Summary
Acute myeloid leukaemia is a cancer of the blood and bone marrow. We have identified new genes that act with the known oncogene FLT3-ITD in myeloid disease. We will examine in detail how these new genes contribute to the development of AML. This will aid in the development of new therapies for groups of AML patients with these mutations.
Defining Genomic Mechanisms Associated With Treatment Response, Drug Resistance And Early Blast Crisis In Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Chronic myeloid leukaemia is a fatal disease if untreated. Most patients now survive with new drugs, but some still rapidly die. I aim to understand these differences by investigating the genetic makeup of patients at diagnosis. Some may have gene mutations that prevent drugs from working effectively. Mutations will be detected using technology that can search more than 30,000 genes at the same time. This work could lead to improved survival for more patients by finding new targets for therapy.
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.
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.
Genetics And Genomics Of Breast And Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$714,745.00
Summary
Our knowledge of the number and nature of the genes involved in breast and ovarian cancer is limited. To rapidly define the critical breast and ovarian cancer-causing genes my laboratory uses an integrative genomics approach whereby information from several genome-wide platforms are combined. A key initiative that will underpin much of our work is Lifepool, which is a unique cohort of 100,000 Victorian women attending BreastScreen that will support a range of research into breast cancer.