NCRI Conference Abstracts
Poster Session A ...Biology of cells and organisms

A4   

Differential expression of genes in disseminated and metastatic tumour cells from patients with metastatic breast cancer

Eitan Amir, Thomas Cawthorn, Reuben Broom, Orit Freedman, David Barth, Dongju Wang, Susan Done, Mark Clemons

Princess Margaret Hospital, Toronto, Canada

Background
The molecular mechanisms underlying the development of bone metastases (BM) in breast cancer remain unclear. Disseminated tumour cells (DTCs) in the bone marrow of breast cancer patients have been identified, but their potential to initiate metastases is not known. We prospectively evaluated the genetic differences between DTCs in the bone marrow and metastatic tumour cells (MTCs) obtained from computed tomography (CT) guided biopsies of radiologically confirmed bone metastases.

Method
Thirteen breast cancer patients with BM underwent a CT-guided BM biopsy and a bone marrow aspiration (for DTCs). Tumour cells were enriched by immunomagnetic separation and RNA was extracted from each sample. Gene expression profiling was conducted using Illumina Human Ref-8 bead arrays comprising 24,500 gene probes. Microarray data was analyzed using BeadStudio software to identify differentially expressed genes. Ingenuity Pathway Analysis software was used to identify genes integral to specific pathways postulated to be involved in cancer metastasis.

Results
A signature of 133 candidate genes differentially expressed between the two sample types was identified.  Paired analysis of samples obtained from the same patient identified a subset of 161 genes, of which 52 overlapped with the initial unmatched signature. Several genes relevant to breast cancer metastasis to bone (i.e. osteopontin, CTGF, parathyroid hormone receptor, EGFR) were significantly overexpressed in MTCs compared to DTCs.

Conclusion
Our results suggest that there are specific subsets of genes required for breast cancer cells to form overt bone metastases. A number of genes identified participate in the vicious cycle model of osteolytic bone metastases formation. This work provides the foundation for further investigation and may aid in the identification of novel therapeutic targets for metastasis inhibition.