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 (e.g. colon and 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 (DCIS)) 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 histology and genetic changes. This correlation is effected using advanced molecular techniques in several ways. Firstly, through tissue microdissection involving laser capture microdissection in some cases, secondly through fluorescence in situ hybridisation (FISH) analysis which allows 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.
For further information, please visit our lab homepage at http://www.uhnres.utoronto.ca/donelab