Colorectal cancer (CRC) is the second most common internal cancer in Australia and the second leading cause of cancer death. Currently more than 14,000 new cases are diagnosed annually in Australia alone, with a worldwide annual incidence of almost a million. Early detection is critical, but unfortunately for 30 – 50% of patients the chances for curative treatment are greatly diminished by the time of diagnosis. For early detection, a better understanding of molecular alterations in CRC precursor lesions and molecular events leading to progression into invasive disease is critical.
Our research explores the serrated pathway of colorectal cancer using innovative and advanced proteomics, gene expression analysis techniques and next generation sequencing technology. A key focus is finding genes that are differentially expressed between the sessile serrated, hyperplastic and conventional adenomatous types of colorectal polyps. We are also seeking to identify biomarkers to support early detection of precursor and early colorectal cancers, and to develop a non-invasive blood based test for detecting colorectal cancer and its precursors.
Current research projects
- Molecular characterisation of serrated pathway neoplasia: 30-40% of cancers develop from “serrated” polyps which until recently were regarded as innocuous. These polyps are difficult to detect colonoscopically and may pose diagnostic dilemmas for pathologists. Using –omics technologies we are exploring the biology of early precursor lesions and the potential factors that influence the rate of progression of these lesions to carcinoma.
- Circulating Tumour DNA in patients with Colorectal Cancer: We have successfully detected somatic BRAF and KRAS mutations in plasma DNA obtained from patients with colorectal cancer where their tumours were characterised on molecular levels using Sequenom MassArray System. We are exploring this technique, assessing its utility as a disease diagnostic, prognostic and monitoring tool.
Caruso M, Fung KYC, Moore J, Brierley GV, Cosgrove LJ, Thomas M, Cheetham G, Brook E, Fraser LM, Tin T, Tran H, Ruszkiewicz A, ‘Claudin 1 expression is elevated in colorectal cancer precursor lesions harbouring the BRAF V600E mutation.’, Translational Oncology (in press)
Dvorak K, Aggeler B, Palting J, McKelvie P, Ruszkiewicz A, Waring P, ‘Immunohistochemistry with the anti-BRAF V600E (VE1) Antibody: Impact of Pre-analytical Conditions and Concordance with DNA Sequencing in Colorectal and Papillary Thyroid Carcinoma’, Pathology (in press)
Hocking C, Hardingham JE, Broadbridge V, Wrin J, Townsend AR, Tebbutt N, Cooper J, Ruszkiewicz A, Lee C, Price TJ., ‘Can we accurately report PTEN status in advanced colorectal cancer?’, BMC Cancer. 2014 Feb 25;14:128.
Winter M, Gibson R, Ruszkiewicz A, Thompson SK, Thierry B., ‘Beyond conventional pathology: Towards preoperative and intraoperative lymph node staging’, Int J Cancer. 2014 Jan 27.
Smith E, Ruszkiewicz AR, Jamieson GG, Drew PA., ‘IGFBP7 is associated with poor prognosis in oesophageal adenocarcinoma and is regulated by promoter DNA methylation’, Br J Cancer. 2014 Feb 4;110(3):775-82.