Oncogenomics - project details

Melanoma

Melanoma is a cancer arising in pigment-producing cells of the skin, which occurs at a high rate in Queensland, and has a very poor prognosis if not diagnosed and treated early. Sunburn and ultraviolet light exposure are key risk factors for melanoma and other skin cancers, but some of the risk of developing these tumours is also inherited in genes. One of our primary objectives is to identify genes that are associated with the risk of melanoma or related traits such as moles, eye and skin colour. We use genome-wide linkage and association scans, and recently have carried out whole-genome sequencing to aid in the search for genes that help explain why some people are more likely to develop melanoma than others. Additionally, we are investigating changes that occur within the melanoma tumours through a combination of array comparative genomic hybridisation, microarray gene expression profiling, microRNA analysis and exome sequencing. These experiments will help us understand the melanoma disease process, which we hope will lead to better ways of diagnosing and treating melanoma in future.

Oesophageal cancer

There are two main forms of oesophageal cancer: squamous cell carcinoma and oesophageal adenocarcinoma, each with their own risk factors and susceptibilities. While the rates of squamous cell carcinoma have remained relatively stable within western populations, including Australia, the rates for oesophageal adenocarcinoma have increased alarmingly over the past few decades. Our main focuses are to improve our understanding of the genetic changes leading to oesophageal adenocarcinoma (in conjunction with David Whiteman's Cancer Control Group, QIMR) and those that relate to cancer prognosis (in conjunction with Andrew Barbour’s lab at the Queensland University Department of Surgery’s Princess Alexandra Hospital campus). We are investigating genome-wide expression, DNA copy number, methylation and mutation profiles within oesophageal tissues collected from adenocarcinoma patients, those with a precancerous tissue known as Barrett’s oesophagus, and those of normal control individuals. Recent data suggest that DNA damage resulting from reflux of stomach acid may be a major contributor to oesophageal adenocarcinoma risk, and that the loss of mechanisms responsible for resisting acid damage may be an early indication of increased cancer risk.

Multiple endocrine neoplasia type 1

We are also interested in the molecular genetics of the cancer syndrome multiple endocrine neoplasia type 1 (MEN 1). People with this syndrome develop tumours in the endocrine hormone-producing cells of the parathyroid, pancreas, and pituitary glands (see picture right). We have found mutations of the MEN1 susceptibility gene in MEN 1 families, as well as in a panel of endocrine tumours. In collaboration with Dr Graham Kay (CCQ Transgenics Laboratory) we have generated total and tissue-specific knockout mouse models to investigate the function of the Men1 gene and the menin protein that it encodes, and to better understand the biology of endocrine tumours. We aim to identify genes that are regulated by menin, and pathways that affect menin, as well as improved understanding of the ways that tumours develop in the pituitary and in the hormone-producing cells of the pancreas.