Research Focus
The Cancer Genetics Laboratory focuses on why some people get breast cancer, and how these cancers develop from a normal cell.
Using genome wide association studies (GWAS) we have identified over 250 breast cancer risk loci. We have successfully identified some of the target genes at several 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 but these might not all contribute to breast cancer risk. We are therefore moving to functional screens to identify the causal genes at risk loci.
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.
Gallery
Research Projects
Current Research Projects
Performing CRISPR functional screens of all the predicted target genes at breast cancer risk loci to identify novel breast cancer risk genes:
Exploring opportunities for drug repositioning from knowledge of the GWAS target genes for prevention and treatment
Evaluating the immune cell composition in peripheral blood from women at elevated risk of breast cancer who subsequently developed breast cancer, compared to women of similar risk who did not
Funding
- The laboratory has been continually supported by NHMRC since 1992
- NHMRC Fellowship, Program, Project, EU, Ideas and Investigator grants
- US Army Department of Defense
- Gray Foundation (USA)
- National Breast Cancer Foundation
- Susan Komen Foundation
Publications
Li … Chenevix-Trench Point mutations in exon 1B of APC reveal gastric adenocarcinoma and proximal polyposis of the stomach as a familial adenomatous polyposis variant American Journal of Human Genetics 98(5):830-842 (2016)
Bojesen … Chenevix-Trench*, Dunning*. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nature Genetics 45:371-84 (2013)
Kuchenbaecker … Chenevix-Trench. Identification of six new susceptibility loci for invasive epithelial ovarian cancer. Nature Genetics 47:164-71 (2015)
Student Projects
Further Information
- Dr Sefi Rosenbluh, Monash University
- Dr Kara Britt, Peter MacCallum Cancer Centre
- Associate Professor Fernando Guimaraes, University of Queensland
- Professor Melissa Southey, Monash University
- Dr Paul James, Peter MacCallum Cancer Centre
- Dr Roger Milne, Cancer Council Victoria
- Professor Sunil Lakhani, University of Queensland
- Professor Doug Easton, Cambridge University
- Professor Antonis Antoniou, Cambridge University
- Dr Kate Nathanson, University of Pennsylvania