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| Status |
Public on Jun 20, 2011 |
| Title |
Genomic analysis identifies unique signatures predictive of brain, lung, and liver relapse |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
The ability to predict metastatic potential is of clinical and biological importance. Numerous metastasis/relapse predictors exist for breast cancer patients; however, what is less well established is whether predicting metastasis to specific organs sites is feasible. In this study we sought to determine: 1) the degree to which gene signatures vary across tumors and their metastases, 2) if genomic intrinsic subtypes associate with particular organs of relapse, and 3) if other genomic signatures can predict spread to specific organs. Using a gene expression microarray data set of >1000 breast tumors and metastases, we observed that >90% of 298 gene signatures were similarly expressed between matched pairs of breast tumors and metastases; those most altered were reflective of cell types including fibroblasts and immune cells. Significant associations were identified between tumor subtypes and organ of first relapse. Among these, HER2-enriched tumors were significantly associated with liver, and Basal-like and Claudin-low tumors with brain and lung. Correspondingly, previously published brain and lung metastasis signatures, along with embryonic stem cell and tumor initiating cell signatures, were also associated with Basal-like and Claudin-low subtypes. These signatures strongly correlated with low Differentiation Scores (DS) and, to a lesser extent, high proliferation. Interestingly, within Basal-like and Claudin-low tumors, low DS further predicted for brain and lung metastases. In total, intrinsic subtype and DS provide clinically useful information that identifies the distant organ sites that should be most closely monitored for signs of disease recurrence.
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| Overall design |
414 samples profiled on Agilent microarrays.
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| |
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| Contributor(s) |
Harrell CJ |
| Citation(s) |
21671017 |
| Submission date |
Dec 28, 2010 |
| Last update date |
Nov 17, 2017 |
| Contact name |
Charles M. Perou |
| E-mail(s) |
cperou@med.unc.edu
|
| Organization name |
University of North Carolina at Chapel Hill
|
| Department |
Professor of Genetics, and Pathology & Laboratory Medicine; Lineberger Comprehensive Cancer Center
|
| Street address |
12-044 Lineberger Comprehensive Cancer Center CB# 7295
|
| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599-7264 |
| Country |
USA |
| |
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| Platforms (7)
|
| GPL885 |
Agilent-011521 Human 1A Microarray G4110A (Feature Number version) |
| GPL887 |
Agilent-012097 Human 1A Microarray (V2) G4110B (Feature Number version) |
| GPL1197 |
Agilent Human 1A Oligo V2+UNC_custom array |
| GPL1390 |
Agilent Human 1A Oligo UNC custom Microarrays |
| GPL1708 |
Agilent-012391 Whole Human Genome Oligo Microarray G4112A (Feature Number version) |
| GPL5325 |
Agilent UNC Perou Lab Homo sapiens 1X44K Custom Array |
| GPL6607 |
Agilent UNC Perou Lab Homo sapiens 1X44k custom with virus probes |
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| Samples (414)
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| Relations |
| BioProject |
PRJNA136915 |
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