Gene expression differences between disseminated tumor cells and tumor cells from overt bone metastases in patients with metastatic breast cancer
| Autor: | Susan J. Done, Dong-Yu Wang, David Barth, D. Gianfelice, J. Galica, Reuben James Broom, Orit Freedman, T. R. Cawthorn, Eitan Amir, Mark Clemons |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty medicine.diagnostic_test business.industry Microarray analysis techniques medicine.disease Immunomagnetic separation Metastatic breast cancer Gene expression profiling medicine.anatomical_structure Breast cancer Circulating tumor cell Oncology Biopsy medicine Bone marrow business |
| Zdroj: | Journal of Clinical Oncology. 27:1040-1040 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2009.27.15_suppl.1040 |
| Popis: | 1040 Background: Despite extensive work evaluating molecular differences between primary tumors, circulating tumor cells, disseminated tumor cells (DTCs) and established metastases, it is not apparent which genetic alterations are required to form viable, independent bone metastases (BM). A major limitation in exploring the genetic differences between DTCs and established BM is the paucity of fresh BM tissue available. Methods: Ten breast cancer patients with BM underwent a CT-guided BM biopsy and a bone marrow aspiration (for DTCs). Tumor 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. 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 involved in tumor dissemination. Results: The yield of analyzable malignant cells from BM and bone marrow aspirates was 60% and 80%, respectively. A signature of 133 genes was identified that was differentially expressed between the two sample types. Paired analysis of samples from the same patients 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 over-expressed in the BM compared to the DTCs. Conclusions: Results suggest that there are specific subsets of genes, which are required for DTCs in the bone marrow to form overt BM. A number of genes identified are already known to participate in osteolytic BM formation. This signature may allow identification of patients at increased risk for developing BM. No significant financial relationships to disclose. |
| Databáze: | OpenAIRE |
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