Functional Analysis Of Relapse Predictive Genes In Wilms Tumour
Funder
National Health and Medical Research Council
Funding Amount
$571,311.00
Summary
Wilms tumor is a paediatric kidney cancer, the most common abdominal tumour seen in children. About 20% of Wilms tumour patients have relapsing fatal tumours. We have found two genes that mark tumours which relapse: C-EBPB and CLK1. Characterization of C-EBPB and CLK1 will yield new information regarding the mechanisms underlying development and progression of Wilms tumours, leading to improved treatment for Wilms tumor patients. Both C-EBPB and CLK1 may also have roles in other human cancers.
Cancer is the result of multiple genetic errors, involving both the overactivity of growth-stimulating oncogenes and the loss of tumour suppressor genes. The identification of the genes in both of these categories is important if we are to understand and intervene in the disease. Tumour suppressors are the more difficult to identify, precisely because they are lost in cancer cells. Normally the task is extremely time consuming, tedious and expensive. We have developed a system which will provide ....Cancer is the result of multiple genetic errors, involving both the overactivity of growth-stimulating oncogenes and the loss of tumour suppressor genes. The identification of the genes in both of these categories is important if we are to understand and intervene in the disease. Tumour suppressors are the more difficult to identify, precisely because they are lost in cancer cells. Normally the task is extremely time consuming, tedious and expensive. We have developed a system which will provide a short-cut to the cloning of one such gene. We have started with the mouse version, which is lost in leukemic cells. We have mapped the gene to within a very small chromosomal region, and we have identified a biological effect which correlates with loss of the gene. Our next step is to combine these two approaches to clone the gene. Because these genes are always highly conserved between species, we will be able to quickly clone the corresponding human gene, the loss of which is very likely to be important in cancer of various types.Read moreRead less
Identification Of A Genetic Defect Characterized By Radiosensitivity And Defective P53 Stabilization
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
Radiation is an important therapeutic agent for the treatment of a variety of cancers. However, radiation also causes cancers, certainly at high doses but it remains unclear as to the threat from low dose radiation eg in the vicinity of radiation accidents and at high altitudes. A greater understanding of the threats of radiation exposure is possible from the study of a number of rare syndromes characterized by extreme sensitivity to radiation and predisposition to develop cancer. The identifica ....Radiation is an important therapeutic agent for the treatment of a variety of cancers. However, radiation also causes cancers, certainly at high doses but it remains unclear as to the threat from low dose radiation eg in the vicinity of radiation accidents and at high altitudes. A greater understanding of the threats of radiation exposure is possible from the study of a number of rare syndromes characterized by extreme sensitivity to radiation and predisposition to develop cancer. The identification of new syndromes with radiosensitivity assists in delineating the overall response to radiation and the connection with cancer. This project is designed to identify the molecular basis of what appears to be a novel defect. It has some of the characteristics of a well described syndrome ataxia-telangiectasia (A-T), namely signs of neurodegeneration and sensitivity to radiation but the protein defective in A-T appears to have normal function in this case. A comprehensive investigation of a number of pathways of radiation signaling is planned to identify the nature of the defect.Read moreRead less
Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the molecular defects which contribute to disease initiation and progression. Over the last twenty years significant progress has been made in this regard, however there still remain a considerable number of unanswered questions. For example, it is not yet clear which are the most critical molecules ....Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the molecular defects which contribute to disease initiation and progression. Over the last twenty years significant progress has been made in this regard, however there still remain a considerable number of unanswered questions. For example, it is not yet clear which are the most critical molecules contributing to this disease and thus which are the best targets for therapeutic intervention. In this proposal, we aim to study two molecules. The first is called BRCA1 and is particularly important in inherited susceptibility to breast cancer. The second is called PML and, although originally described as a leukaemia-associated gene, it has since been implicated in a number of cancers. Specifically, we aim to investigate the possibility that PML and BRCA1 work together to protect against cancer and that they do this by regulating the ends of chromosomes, that is, the telomeres.Read moreRead less