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Status |
Public on Jul 06, 2012 |
Title |
Mechanisms and pathways of bone metastasis: challenges and pitfalls of performing molecular research on patient samples |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
The molecular mechanisms underlying the development of bone metastases in breast cancer remain unclear. Disseminated tumour cells (DTCs) in the bone marrow of breast cancer patients are commonly identified, even in early stage disease, but their potential to initiate metastases is not known. The mechanism whereby DTCs become overt metastatic tumour cells (MTCs) is therefore, an area of considerable interest. This study explored the analysable yield of genetic material from human biopsy samples in order to describe differences in gene expression between DTCs and bone MTCs. Thirteen breast cancer patients with bone metastases underwent a CT-guided bone metastasis biopsy and a bone marrow biopsy. Tumour cells were enriched and gene expression profiling was conducted to identify differentially expressed genes. The analysable yield of sufficient RNA for microarray analysis was 60% from bone metastasis biopsies and 80% from bone marrow biopsies. A signature of 133 candidate genes differentially expressed between DTCs and MTCs was identified. Several genes relevant to breast cancer metastasis to bone (osteopontin, CTGF, parathyroid hormone receptor, EGFR) were significantly overexpressed in MTCs as compared to DTCs. Biopsies of bone metastases and bone marrow rarely yield enough tissue for robust molecular biology studies using clinical samples. The findings obtained however are interesting and seem to overlap with the bone metastasis gene expression signature described in murine xenograft models. Larger biopsy specimens or improved RNA extraction techniques may improve analysable yield and feasibility of these techniques.
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Overall design |
Gene expression profiling was utilized to compare DTCs obtained from bone marrow aspirates (A) to MTCs isolated from Computed Tomography (C) guided biopsies of bone metastases.
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Contributor(s) |
Wang DY, Cawthorn TR, Done SJ, Clemons M |
Citation(s) |
19697143 |
Submission date |
Feb 10, 2009 |
Last update date |
Mar 20, 2017 |
Contact name |
Dong-Yu Wang |
Organization name |
UHN-PMH-OCI
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Street address |
610 University Ave
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City |
Toronto |
ZIP/Postal code |
M5G 2M9 |
Country |
Canada |
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Platforms (1) |
GPL6883 |
Illumina HumanRef-8 v3.0 expression beadchip |
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Samples (14)
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GSM368877 |
DTCs (bone marrow aspirates) from Patient 1 (4424556026_A) |
GSM368878 |
DTCs (bone marrow aspirates) from Patient 2 (4424556026_B) |
GSM368879 |
DTCs (bone marrow aspirates) from Patient 4 (4424556026_C) |
GSM368880 |
DTCs (bone marrow aspirates) from Patient 6 (4424556026_D) |
GSM368881 |
MTCs (Computed Tomography) from Patient 3 (4424556026_E) |
GSM368882 |
MTCs (Computed Tomography) from Patient 8 (4424556026_F) |
GSM368883 |
MTCs (Computed Tomography) from Patient 10 (4424556026_G) |
GSM368884 |
DTCs (bone marrow aspirates) from Patient 7 (4424556027_A) |
GSM368885 |
DTCs (bone marrow aspirates) from Patient 8 (4424556027_B) |
GSM368886 |
DTCs (bone marrow aspirates) from Patient 11 (4424556027_C) |
GSM368887 |
DTCs (bone marrow aspirates) from Patient 13 (4424556027_D) |
GSM368888 |
MTCs (Computed Tomography) from Patient 11 (4424556027_E) |
GSM368889 |
MTCs (Computed Tomography) from Patient 12 (4424556027_F) |
GSM368890 |
MTCs (Computed Tomography) from Patient 13 (4424556027_G) |
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Relations |
BioProject |
PRJNA112323 |