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| Status |
Public on Oct 22, 2018 |
| Title |
DNA methylation of two triple-negative patient-derived breast cancer xenografts |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
|
| Summary |
All-trans retinoic acid (atRA) regulates gene expression and is used to treat acute promyelocytic leukemia. Attempts to use atRA for breast cancer treatment without a stratification strategy have resulted in limited overall effectiveness. To identify biomarkers for the treatment of triple-negative breast cancer (TNBC) with atRA, we characterized the effects of atRA on the tumor growth of 13 TNBC cell lines. This resulted in a range of tumor growth effects that was not predictable based on the levels of retinoid signaling molecules and transcriptional responses that were mostly independent of retinoic acid response elements. Given the importance of DNA methylation in regulating gene expression, we hypothesized that differential DNA methylation could predict the response of TNBCs to atRA. We identified over 1400 CpG sites that were differentially methylated between atRA resistant and sensitive cell lines. These CpG sites predicted the response of four TNBC patient-derived xenografts to atRA treatment and we utilized these xenografts to refine the profile to 6 CpGs. We identify as many as 17% of TNBC patients who could benefit from atRA treatment. These data illustrate that differential DNA methylation of specific sites may predict the response of patient tumors to atRA treatment.
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| Overall design |
Two independent PDXs were propagated in mice prior to DNA isolation and DNA methylation determination
2 samples analyzed, 1 replicate.
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| Contributor(s) |
Coyle KM, Dean C, Thomas ML, Vidovic D, Giacomantonio CA, Helyer L, Marcato P |
| Citation(s) |
30352973 |
| Submission date |
Jul 31, 2018 |
| Last update date |
Jan 21, 2019 |
| Contact name |
Paola Marcato |
| Organization name |
Dalhousie University
|
| Department |
Pathology
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| Street address |
PO Box 15000
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| City |
Halifax |
| State/province |
Nova Scotia |
| ZIP/Postal code |
B3H 4R2 |
| Country |
Canada |
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| Platforms (1) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE118003 |
Expression profiling and DNA methylation of TNBCs |
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| Relations |
| BioProject |
PRJNA483984 |
