Metastasis initiation is a complex process encompassing numerous steps. To identify molecular alterations associated with early and late stages of metastasis, we used high throughput screening techniques. Early events in metastasis were investigated by differential proteomic analysis of lymph node-negative and positive breast cancer samples. Two candidate biomarkers (DCN and HSP90B1) were discovered and further validated through tissue microarray analyses. To examine late events in metastasis formation, we prospectively evaluated genomic differences between disseminated tumour cells in bone marrow, and metastatic tumour cells obtained from computed tomography guided biopsies of bone metastases. Results indicate that specific subsets of genes are required for breast cancer cells to initiate bone metastases. Discovery of proteomic and genomic alterations specifically associated with metastases may yield biomarkers capable of stratifying patients into different risk categories. Proteins and genes identified in this work may form the foundation of a biomarker panel for metastatic risk assessment.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/18239 |
| Date | 12 January 2010 |
| Creators | Cawthorn, Thomas |
| Contributors | Done, Susan Jane |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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