 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 20, 2019 |
| Title |
Myoepithelial cell perturbations in BRCA mutation carriers and in DCIS (ductal carcinoma in situ) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
We describe the gene expression profiles and enhancer landscape of normal myoepithelial cells and perturbations of these in BRCA1 and BRCA2 mutation carriers and in DCIS. We identified a myoepithelial transcription regulatory network orchestrated by p63 and TCF7 and defined the genomic targets of these transcription factors by ChIP-seq. While the majority of myoepithelial cells co-express p63 and TCF7 in normal breast of healthy women, the frequency of these cells is significantly lower in BRCA1 mutation carriers and in DCIS. Downregulation of p63 in MCF10DCIS cells leads to loss of myoepithelial cells and invasive tumors, whereas overexpression of TCF7 enhances tumor growth. Our findings suggest that loss of normal myoepithelial cell function facilitates in situ to invasive carcinoma transition and it may also enhance tumor initiation in BRCA mutation carriers.
|
| |
|
| Overall design |
RNAseq of CD10+ cells from normal breast and DCIS to compare the expression difference in myoepithelial cells.
RNAseq in cell lines with p63 knockdown or TCF7 overexpression to see the genes and pathways regulated by p63 or TCF7.
ChIPseq for p63 and TCF7 to identify their targets and epigenetic landscaping.
H3K27ac ChIPseq of breast organoids from normal (control) woman and BRCA mutation carriers.
|
| |
|
| Contributor(s) |
Ding L, Su Y, Qiu X, Ekram M, Huh SJ, Bloushtain-Qimron N, Harper NW, Jovanovic B, Hines WC, Zi X, Merino VF, Choudhury S, Ethington G, Panos L, Grant M, Rosson GD, Clark J, Herlihy W, Au A, Richardson AL, Argani P, Hwang ES, Fan R, Allred DC, Bobolis K, Kleer C, Blum JL, Long H, Sukumar S, Park SY, Garber JE, Yao J, Bissell M, Polyak K |
| Citation(s) |
31519911 |
| Submission date |
May 01, 2018 |
| Last update date |
Nov 19, 2019 |
| Contact name |
Kornelia Polyak |
| E-mail(s) |
kornelia_polyak@dfci.harvard.edu
|
| Phone |
617-632-2106
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Medical Oncology
|
| Lab |
Polyak
|
| Street address |
450 Brookline Ave
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
|
| Samples (54)
|
|
| Relations |
| BioProject |
PRJNA454454 |
| SRA |
SRP144189 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE113909_RAW.tar |
8.7 Mb |
(http)(custom) |
TAR (of BED, NARROWPEAK, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...