Epigenetics Laboratory

Team Leader
Dr Megan Hitchins

Main Interest Area
The main focus of the Epigenetics Laboratory is to determine the causative role of "germline epimutations" in various familial cancer syndromes, the inheritance pattern associated with this novel "epigenetic" defect, as well as the mechanisms underlying it.

Current projects being conducted by the group include:

1. The Laboratories within the ICR group have previously shown that "germline epimutations" of the cancer-prevention gene, MLH1, cause bowel and uterine cancers at a young age. Usually individuals with this cancer syndrome (hereditary non-polyposis colorectal cancer) have a mutation (spelling mistake) within the genetic code of this gene, which can be transmitted faithfully from one generation. However, we showed that some individuals have a normal MLH1 gene sequence, but instead have a 'coat' of the chemical called CpG methylation, termed a germline epimutation, which causes the gene to be paralysed (Link to Suter et al, Nat Genet and Hitchins et al, Gastroenterology). We have shown that this defect can be transmitted from one generation to the next in a non-Mendelian pattern (link to Hitchins et al. N Engl J Med). The Epigenetics Laboratory now seeks to determine the molecular mechanisms that underlie the formation of germline epimutations of MLH1, and how they are transmitted to a proportion of children. We are also testing patient cell lines with drugs that target the CpG methylation coat to determine if the defect can be reversed to restore gene function.
   
   
2. Having demonstrated the aetiological role of germline epimutations of MLH1 in bowel and uterine cancers, the Epigenetics Laboratory now wish to determine whether this nocel defect affects other cancer-related genes as well. Through national and international collaborators, we are screening individuals with other familial cancer syndromes including familial breast and ovarian cancer, hamartomatous tumours, Peutz-Jeghers syndrome and Von-Hippel Lindau syndrome who do not appear to have a spelling mistake within the respective cancer-causing gene to determine whether germline epimutations are responsible for their cancer.
   
   Sponsors: Dr Megan Hitchins is funded by the Cancer Institute of NSW on a Career Development Fellowship and NHMRC Project Grant. Dr Hitchins has previously been funded by the Cure Cancer Australia Foundation.