MA, MB, BChir, MBA, PhD, FRCPC, FCAP, FRCPath, FCCMG
Dr. Susan J. Done completed her medical training at Cambridge University and then moved to Canada where she is currently an Associate Professor in the Departments of Laboratory Medicine and Pathobiology, and Medical Biophysics, at the University of Toronto.
She is a pathologist at the University Health Network (which includes Toronto General Hospital and the Princess Margaret Cancer Centre) and a member of the Campbell Family Institute for Breast Cancer Research.
Her research is focused on breast cancer intratumoural heterogeneity, circulating tumour markers, and early events in invasion and metastasis.
In our lab the primary focus is the identification and characterization of molecular alterations that lead to the development of solid cancers, particularly breast cancer. It is believed that the study of these changes will lead to the identification of potential diagnostic, prognostic and predictive markers and also therapeutic targets.
Cancer results from a progressive accumulation of genetic alterations. In some organ systems (eg, colon, cervix) it has been demonstrated that these increasing degrees of genetic perturbation are accompanied by increasing degrees of histologic dysplasia. Other tissues are less accessible making the establishment of these links more difficult.
In the breast, certain preneoplastic and preinvasive lesions (hyperplasias and ductal carcinoma in situ) have been linked to invasive breast cancer by the increased relative risk of future invasive disease they confer. However, it has not been clearly established whether these lesions have the potential to progress to invasive breast cancer or are merely markers of increased risk. Advances in tissue microdissection and PCR technologies have made possible the study of molecular alterations in these small, histologically defined lesions.
We believe it is important to localize particular genetic aberrations to specific cells thereby enabling a correlation between histologic and genetic changes. This correlation is effected using advanced molecular techniques in several ways: firstly, tissue microdissection involving laser capture microdissection can be used in some cases; and secondly, fluorescence in situ hybridization (FISH) analysis can allow detection of gene copy number in specific cells.
Current projects in the lab involve the use of gene microarray chips to identify genes and chromosomal regions that are amplified or deleted in the transition from preinvasive to invasive breast cancer and determination of the extent of genomic instability in histologically normal tissue adjacent to invasive carcinoma.
My lab primarily focuses on the identification and characterization of molecular alterations leading to the development and progression of solid cancers, particularly breast cancer. Study of these changes at both the genetic and protein level will lead to the identification of potential diagnostic, prognostic, and predictive markers. Such markers may also prove useful as potential therapeutic targets.
Cancer results from the progressive accumulation of genetic alterations. In some organ systems (i.e. colon and cervix), it has been demonstrated that increasing degrees of genetic perturbation are also accompanied by increasing degrees of histologic dysplasia. Other tissues are less accessible, making definitive establishment of these links more difficult. In the breast, the appearance of certain pre-neoplastic and pre-invasive lesions has been linked to the development of invasive cancer through an increase in relative risk. However, it has yet to be clearly established whether or not all these lesions have the potential to progress to invasive breast cancer, or are merely markers of increased risk. Our study of morphologically normal breast tissue and various stages of cancer progression in different subtypes of breast cancer will provide insights into the key events that occur as breast cancer develops and evolves.
Selected list of publications
Kanwar N., Hu P., Bedard P., Clemons M., McCready D and Done S.J. Identification of Genomic Signatures in Circulating Tumour Cells from Breast Cancer. INT J CANCER (2015) 137:332-44. Epub12 Jan 2015
Prummel M.V., Muradali D., Shumak R., Majpruz V., Brown P., Jiang H., Done S.J., Yaffe M.J. and Chiarelli A.M. Digital compared with screen-film mammography: Measures of diagnostic accuracy among women screened in the Ontario Breast Screening Program RADIOLOGY (2016) 278:365-73. Epub 2 Sep 2015
Liu F.F., Shi W., Done S.J., Miller N., Pintilie M., Voduc D., Nielsen T.O., Nofech-Moses S., Chang M.C., Whelan T.J., Weir L.M., Olivotto I.A., McCready D.R. and Fyles A.W. Identification of a low-risk Luminal A breast cancer cohort that may not benefit from breast radiotherapy. JOURNAL OF CLINCIAL ONCOLOGY (2015) 33:2035-40. Epub 11 May 2015
Harris I.S., Treoar A.E., Inoue S., Sasaki M., Gorrini C., Lee K.C., Yung K.Y., Brenner D., Knobbe-Thomsen C.B., Cox M.A., Elia A., Berger T., Cescon D.W., Adeoye A., Brüstle A., Molyneux S.D., Mason J.M., Li W.Y., Yamamoto K., Wakeham A., Berman H.K., Khokha R., Done S.J., Kavanagh T.J., Lam C.W. and Mak T.W. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. CANCER CELL (2015) 27:211-22.Epub 22 Jan 2015
Rahbar R., Li A., Ghazarian M., Yau H.L., Paramathas S., Lang P.A., Schildknecht A., Elford A.R., Garcia-Batres C., Martin B., Berman H.K., Leong W.L., McCready D.R., Reedijk M., Done S.J, Miller N., Youngson B., Suh W.K., Mak T.W. and Ohashi P.S. B7-H4 expression by nonhematopoietic cells in the tumour microenvironment promotes antitumor immunity. CANCER IMMUNOL RES (2015) 3:184-95. Epub 19 Dec 2014
Lam K., Chan C., Done S.J., Levine M.N. and Reilly R.M. Preclinical pharmacokinetics, biodistribution, radiation dosimetry and acute toxicity studies required for regulatory approval of a Clinical Trial Application for a Phase I/II clinical trial of (111)In-BzDTPA-pertuzumab. NUCL MED BIOL (2015) 42:78-84. Epub 14 Oct 2014
Cappello P., Blaser H., Gorrini C., Lin D.C., Elia A.J., Wakeham A., Haider S., Boutros P.C., Mason J.M., Miller N.A., Youngson B., Done S.J. and Mak T.W. Role of Nek2 on centrosome duplication and aneuploidy in breast cancer cells. ONCOGENE (2014) 33: 2375-84. Epub 27 May 2013.
Chiarelli A., Edwards S.A., Prummel M.V., Muradeli D., Majpruz V., Done S.J., Brown P., Shumak R.S. and Jaffe M.J. Digital Compared to Screen-Film Mammography: Performance Measures in Concurrent Cohorts within an Organized Breast Screening Program. RADIOLOGY (2013) 268: 684-93. E-pub 14 May 2013.
Harris I.S., Blaser H., Moreno J., Treloar A.E., Gorrini C., Sasaki M., Mason J.M., Knobbe C.B., Rufini A., Halle M., Elia A.J., Wakeham A., Tremblay M.L. Melino G., Done S. and Mak T.W. PTPN12 promotes resistance to oxidative stress and supports tumorigenesis by regulating FOXO signaling. ONCOGENE (2014) 33: 1047-54. Epub 25 Feb 2013.
Khoumais N.A., Scaranelo A.M., Moshonov H., Kulkarni S.R., Miller N., McCready D.R., Crystal P. and Done S.J. Incidence of Breast Cancer in Patients with Pure Flat Epithelial Atypia Diagnosed at Core Needle Biopsy of the Breast. ANN SURG ONCOL (2013) 20: 133-8. Epub 12 Oct 2012.
Quail DF., Walsh L.A., Zhang G., Findlay S.D., Moreno J., Fing L., Ablack A., Lewis J.D., Done S.J. Hess D.A. and Postovit L.-M.. Embryonic protein Nodal promotes breast cancer vascularisation. CANCER RESEARCH (2012) 72: 3851-63.
Chio I.I., Sasaki M., Ghazarian D., Moreno J., Done S., Ueda T., Inoue S., Chang Y.L., Chan N.J., Mak T.W. TRADD contributes to tumour suppression by regulating ULF-dependent p19(Arf) ubiquitylation. NAT. CELL BIOL (2012) 14: 625-33. May 6. doi: 10.1038/ncb2496. Epub ahead of print
Xu C., Tran-Thanh D., Ma C., May K., Jung J., Vecchiarelli J. and Done S.J. Mitochondrial D310 Mutations in the Early Development of Breast Cancer BRITISH JOURNAL OF CANCER (2012) 106: 1506-11. Epub 3 Apr 2012.
Cawthorn T.R., Moreno J.C., Dharsee N., Tran-Thanh D., Ackloo S., Zhu P.H., Sardana G., Chen J., Kupchak P., Jacks L.M., Miller N.A., Youngson B.J., Iakovelv V., Guidos C., Vallis K.A., Evans K.R., McCready D., Leong W.L and Done S.J. Proteomic analyses reveal high expression of Decorin and Endoplasmin (HSP90B1) are associated with breast cancer metastasis and decreased survival. PLoS ONE. (2012) 7(2): e30992. doi:10.1371/journal.pone.0030992. Epub 20 Feb 2012.
Arneson N., Moreno J., Iakovlev V., Ghazani A., Warren K., McCready D., Jurisica I. and Done S.J. Comparison of Whole Genome Amplification Methods for Analysis of DNA Extracted from Microdissected Early Breast Lesions in Formalin Fixed Paraffin Embedded Tissue. ISRN Oncology. (2012) 2012:710692. Epub 14 Mar 2012.
Honours and Awards
Name: Sustained Excellence Education Award, Department of Laboratory Medicine & Pathobiology, University of Toronto (2021)