Analysis Of Circulating Tumour DNA For Mutational Characterisation And Tracking Disease Progression In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$908,676.00
Summary
Multiple myeloma is cancer of plasma cells in the bone marrow and presents at multiple sites with dissimilar genetic information (GI) across these sites. Invasive biopsies of multiple sites are required to determine the GI. Cancer cells shed small amounts of DNA into the blood stream and this circulating DNA (ctDNA) contains GI from multiple cancer sites. This project will evaluate the utility of ctDNA to determine GI and to predict treatment response in MM patients.
Co-operation Between GATA2 Mutation Or Expression And RAS Signalling In AML
Funder
National Health and Medical Research Council
Funding Amount
$860,601.00
Summary
We have identified a gene GATA2 which, when mutated, can lead to leukaemia (blood cancer). We will collect samples worldwide from families and individuals that carry GATA2 mutations and have developed leukaemia, and will screen for other genetic changes that contribute to leukaemia. We have also identified a novel group of patients who have a low GATA2 activity and who also have mutations in the RAS gene, a known contributor to leukaemia. We will determine how these cooperate to cause leukaemia.
Identifying Early Molecular Changes Underlying Familial Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$755,793.00
Summary
Analysis of our unique genetic model of inherited, familial Alzheimer’s disease (fAD) using advanced molecular, computational and behavioural techniques is revealing dramatic, early changes in brain function long before the disease would occur. We will expand our work to compare our first model with a model of the most common fAD mutation E280A “Paisa” from Columbia. Commonalities between the models will help us identify the initial stresses that cause Alzheimer’s disease.
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.
Targeting The EGFR And C-Met Tyrosine Kinase Receptors In Myeloproliferative Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$607,559.00
Summary
We propose that in the blood disorders called Myeloproliferative Neoplasms (MPN) there are important changes that affect the function of receptors expressed on the surface of blood cells. These changes will perturb blood cell production and may be able to be targeted effectively with drugs. We will test this using laboratory-based and mouse models of MPN, together with specific drugs that are currently in the clinic, and that inhibit the activity of the key receptors involved. This approach can ....We propose that in the blood disorders called Myeloproliferative Neoplasms (MPN) there are important changes that affect the function of receptors expressed on the surface of blood cells. These changes will perturb blood cell production and may be able to be targeted effectively with drugs. We will test this using laboratory-based and mouse models of MPN, together with specific drugs that are currently in the clinic, and that inhibit the activity of the key receptors involved. This approach can be rapidly translated to clinical trial.Read moreRead less
Assessment Of Markers Of Genomic Instability For The Prediction Of Treatment Response In Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$590,086.00
Summary
The success of therapy for patients with chronic myeloid leukaemia depends on close monitoring during therapy for early recognition of pending relapse, and the selection of appropriate treatment if drug resistance occurs. This project aims to identify patients at the start of therapy who are at risk of treatment failure by investigating their genetic profile. An increased frequency of gene mutations may indicate that patients require more aggressive therapy to achieve an optimal response.
Molecular Markers Of Relapse And Treatment Response In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$539,535.00
Summary
Ovarian cancer is a complex disease with generally poor long-term survival. Response to initial treatment is generally high however most women relapse, usually within 2 years. Response to chemotherapy is variable and difficult to predict. This project will focus on why ovarian cancer recurs, especially after a good initial response; on understanding what features determine response to chemotherapy once patients have relapsed; and on strategies to increase response to chemotherapy.
Identifying The Mechanism Of The G2 Phase UV Checkpoint And Repair Response Commonly Defective In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$569,656.00
Summary
The UV component of sunlight is the major environmental factor driving the development of melanoma. UV radiation can directly mutate genes resulting in their inability to perform normal functions which may contribute to cancer. Despite the high number of mutations directly attributable to UV radiation, the mechanisms known to repair these mutations are generally normal in melanoma. This research will investigate a repair mechanism we have identified that is commonly defective in melanomas.
Defining The Leukaemogenic Mechanism For GATA2 T354M, A New Predisposing Mutation In Familial MDS/AML
Funder
National Health and Medical Research Council
Funding Amount
$631,883.00
Summary
A successful approach for identification of cancer genes has been to study the 5-10% of cases occurring in families with inherited predisposition to develop cancer. Unlike solid tumours, few cancer-causing mutations are known for haematological cancers. We have found a new mutation in 3 families in a gene (GATA2) not previously associated with familial acute myeloid leukaemia. We will explore how this mutation causes leukaemia to help better understand the more common non-inherited leukaemias.
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.