The Gorringe lab focuses on cancer precision medicine: applying genomics to clinical questions in breast and ovarian cancers.
Personalized Risk Evaluation in breast Ductal Carcinoma in situ (PRECISION)
Ductal carcinoma in situ (DCIS) accounts for 20-25% of breast cancer and is a growing health problem, with great variation in treatment and outcome. After local excision, about 25% of DCIS will recur. There are no robust markers of recurrence risk for tailoring treatment to optimise patient outcome and minimise treatment toxicity. Thus, clinical management of DCIS is challenging and many women are over-treated while others might benefit from more intense therapy or monitoring. We aim to develop a clinical test for personalised DCIS recurrence risk, using gene copy number, immunohistochemistry and gene expression assays. This study will leverage unique local and international DCIS cohorts that have extensive clinical annotation and follow-up data. A similar study for benign breast lesions (atypical ductal hyperplasia and papillomas) is also being undertaken.
Genomic characterisation of rare ovarian epithelial carcinoma subtypes
While the genomic profiles of high-grade serous carcinomas have been extensively studied, little is known about the low-grade serous and mucinous subtypes. A major current initiative is the comprehensive Genomic Analysis of Mucinous Tumours (GAMuT) study, which analyses primary ovarian and extra-ovarian metastases with mucinous histology using copy number, expression and exome sequencing. The goals are to identify novel targets for therapy and to determine whether mucinous tumours from multiple tissue origins share genomic characteristics. A similar project is underway in low-grade serous carcinomas.
Investigation of GAB2 as a biomarker for therapy response in ovarian cancer
Targeted therapies offer new hope for ovarian cancer, and the PI3K/mTOR/AKT pathway is an area of intense drug development. We identified GAB2 as a candidate biomarker of response to PI3K/mTOR/AKT inhibition in ovarian cancer. This protein, a key component of the pathway that mediates signals from receptor tyrosine kinases to downstream components, shows high expression in cell lines that are sensitive to inhibition. We will evaluate whether GAB2 determines cellular sensitivity to PI3K/mTOR/AKT inhibition.
Gorringe KL, Hunter SM, Pang JM, Opeskin K, Hill P, Rowley SM, Choong DY, Thompson ER, Dobrovic A, Fox SB, Mann GB, Campbell IG (2015). Copy number analysis of ductal carcinoma in situ with and without recurrence. Mod Pathol.28(9):1174-84.
Hunter SM, Anglesio MS, Ryland GL, Sharma R, Chiew YE, Rowley SM, Doyle MA, Li J, Gilks CB, Moss P, Allan PE, Stephens AN, Huntsman DG, deFazio A, Bowtell DD, Australian Ovarian Cancer Study Group, Gorringe KL, Campbell IG (2015). Molecular profiling of low grade serous ovarian tumours identifies novel candidate driver genes. Oncotarget.6(35):37663-77.
Davis, SJ, Sheppard KE, Anglesio MA, George J, Traficante N, Fereday S, Intermaggio MP, Menon U, Gentry-Maharaj A, Lubinksi J, Gronwald J, Pearce CL, Pike MC, Wu A, Kommoss S, Pfisterer J, du Bois A, Hilpert F, Ramus SJ, Bowtell DDL, Huntsman DG, Pearson RB, Simpson KJ, Campbell IG, Gorringe KL (2015). Enhanced GAB2 expression is associated with improved survival in high-grade serous ovarian cancer and sensitivity to PI3K inhibition. Mol Cancer Ther.14(6):1495-503.
Ryland GL, Hunter SM, Doyle MA, Caramia F, Li J, Rowley SM, Christie M, Allan PE, Stephens AN, Bowtell DD, Australian Ovarian Cancer Study Group, Campbell IG, Gorringe KL (2015). Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors. Genome Med.7(1):87.
Ryland GL, Hunter SM, Doyle MA, Rowley SM, Christie M, Allan PE, Bowtell DD, Australian Ovarian Cancer Study Group, Gorringe KL, Campbell IG (2013). RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary. J Pathol.229(3):469-76.
Li J, Lupat R, Amarasinghe KC, Thompson ER, Doyle MA, Ryland GL, Tothill RW, Halgamuge SK, Campbell IG, Gorringe KL (2012). CONTRA: copy number analysis for targeted resequencing. Bioinformatics.28(10):1307-13.