The Gorringe lab focuses on cancer precision medicine: applying genomics to clinical questions in breast and ovarian cancers.
The guiding principle of our research is that the best health outcomes are attained when our understanding of the disease is deep enough to give treatment tailored to the individual. Such personalisation encompasses: accurate diagnosis, to be sure of what condition the individual actually has, including cell of origin; an accurate prognosis, to match the aggressiveness of treatment to the risk of recurrence; and an accurately targeted therapy, to give the patient the best chance of recovery with minimal harm from treatment.
The Gorringe lab has an extensive genomics research program to address key precision medicine issues in women’s cancers, including early breast disease and rare ovarian cancer subtypes.
Research projects
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.
Understanding rare ovarian epithelial carcinoma subtypes to improve outcomes
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.
In addition, we are generating novel in vitro (organoid) and in vivo models for these rare diseases in order to test novel therapies and functionally characterise putative cancer genes.
People
Key publications
Kang EY, Cheasley D, [40 other co-authors] Köbel K, and Gorringe KL. (2021) Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses. Modern Pathology, 34(1):194-206.
Cheasley D, Nigam A, Zethoven M, Hunter SM, Etemadmoghadam D, Semple T, Allan P, Carey MS, Fernandez ML, Dawson A, Köbel M, Huntsman DG, Le Page C, Mes-Masson AM, Provencher D, Hacker N, Gao Y, Bowtell DDL, DeFazio A, Gorringe KL*, Campbell IG*. (2021) Genomic analysis of low-grade serous ovarian carcinoma to identify key drivers and therapeutic vulnerabilities. J. Pathology, 253(1):41-54. (*Co-senior author)
Kader T, Elder K, Zethoven M, Semple T, Hill P, Goode DL, Cheasley D, Rowley SM, Byrne DJ, Pang JB, Miligy IM, Green AR, Rakha EA, Fox SB, Mann GB, Campbell IG, Gorringe KL. (2020) The genetic architecture of breast papillary lesions as a predictor of progression to carcinoma. npj Breast Cancer, 6:9.
Gorringe KL, Cheasley D, Wakefield MJ...[30 other co-authors]… Antill YC, Campbell IG, Scott CL. (2020) Therapeutic options for mucinous ovarian carcinoma. Gynecologic Oncology, 156(3):552-560.
Cheasley D, Devereux L, Hughes S, Nickson C, Procopio P, Lee G, Li N, Pridmore V, Elder K, Mann GB, Kader T, Rowley SM, Fox SB, Byrne D, Saunders H, Fujihara K, Lim B, Gorringe KL*, and Campbell IG*. (2020) The TP53 mutation rate differs in breast cancers that arise in women with high or low mammographic density. npj Breast Cancer 6:34. (*Co-senior author)
Kader T, Hill P, Zethoven M, Goode DL, Elder K, Thio N, Doyle M, Semple T, Sufyan W, Byrne DJ, Pang JB, Murugasu A, Miligy IM, Green AR, Rakha EA, Fox SB, Mann GB, Campbell IG, Gorringe KL. (2019) Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma. J Pathology. 248(3):326-338.
Cheasley D, Wakefield MJ, Ryland GL, [59 other co-authors], Antill YC, Scott CL, Campbell IG, Gorringe KL. (2019) The Molecular Origin and Taxonomy of Mucinous Ovarian Carcinoma. Nature Communications. 10(1):3935.
Pang JB, Savas P, Fellowes AP, Mir Arnau G, Kader T, Vedururu R, Hewitt C, Takano EA, Byrne DJ, Choong DY, Millar EK, Lee CS, O'Toole SA, Lakhani SR, Cummings MC, Mann GB, Campbell IG, Dobrovic A, Loi S, Gorringe KL*, Fox SB*. (2017) Breast ductal carcinoma in situ carry mutational driver events representative of invasive breast cancer. Mod Pathol. 30(7):952-963. (*Co-senior author)
Hendry S, Pang JB, Byrne DJ, Lakhani SR, Cummings MC, Campbell IG, Mann GB, Gorringe KL*, Fox SB*. (2017) Relationship of the Breast Ductal Carcinoma In Situ Immune Microenvironment with Clinicopathological and Genetic Features. Clin Cancer Res. 23(17):5210-5217. (*Co-senior author)
Kader T, Goode DL, Wong SQ, Connaughton J, Rowley SM, Devereux L, Byrne D, Fox SB, Mir Arnau G, Tothill RW, Campbell IG, Gorringe KL. (2016) Copy number analysis by low coverage whole genome sequencing using ultra low-input DNA from formalin-fixed paraffin embedded tumor tissue. Genome Med. 8(1):121.
