In the Cancer Genetics Laboratory we investigate why some people get cancer, and how these cancers, particularly those of the breast and ovary, develop from a normal cell. Using genome wide association studies (GWAS) we have identified 179 breast cancer (BC) risk loci. Through extensive in vitro assays, we and our collaborators have successfully identified some of the target genes at 14 of these loci. The functional mechanism behind the associations usually involves perturbed regulation of target gene transcription by risk single nucleotide polymorphisms (SNPs) lying in regulatory elements positioned some distance from the target. The nearest gene to the GWAS ‘hit’ is not necessarily the target of the association, and for some loci there are multiple gene targets. We have developed a pipeline for predicting target genes at GWAS hits but the challenge of functionally interrogating each risk locus to identify the target gene(s) is enormous. With our collaborator, Dr Sefi Rosenbluh at Monash University, we are now planning to perform large scale pooled CRISPR knockout and activation screens of all the predicted target coding and non-coding genes at these loci to identify novel breast cancer risk genes. We are currently developing assays to identify genes that impact on proliferation, anchorage independence, senescence, tumorigenicity and immunosurveillance. In addition, we will comprehensively investigate breast cancer risk loci where the predicted target genes are known drug targets, with a view to developing novel risk reduction medications.
We also have an interest in genes involved in response to chemotherapy in ovarian cancer patients, and have done a genome-wide association study in cases from the Ovarian Association Consortium. This has identified a locus near the ULK1 gene which is associated with progression free survival in ovarian cancer patients. Further characterization of this locus is underway.
Senior Scientist: Professor Georgia Chenevix-Trench
- Dr Jonathan Beesley, Senior Research Officer
- Dr Jun Jun Li, Research Officer
- Dr Karen McCue, Research Officer
- Dr Wei Shi, Research Officer
- Dr Xiao Qing Chen, Lab Manager and Research Assistant
- Anna Marsh, Research Assistant
- Martina Toso, PhD Student
More information for students:
- Germline variation underlying individual differences in risk of, and outcome from, breast and ovarian cancer
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