|
Status |
Public on Jun 08, 2016 |
Title |
Emergence of neural crest identity is a key early step in melanoma formation [ChIP-Seq] |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
Summary |
The “cancerized field” concept posits that cells of a given tissue share a potentially oncogenic mutation or insult and are thus cancer-prone, yet only discreet clones within the field initiate tumor formation. In melanoma, tumors frequently (~50%) carry the oncogenic BRAFV600E mutation that is also nearly always present in benign nevi that rarely become melanoma. The zebrafish crestin gene is expressed embryonically in neural crest progenitors and is then specifically re-expressed in melanoma tumors. Here, we show by live imaging transgenic zebrafish crestin reporters that single melanocytes in a cancerized field with oncogenic BRAFV600E and p53 tumor suppressor loss undergo a change that recapitulates the neural crest progenitor (NCP) state, and patches of these cells initiate early melanoma. The crestin element is regulated by the NCP transcription factor sox10. Forced sox10 overexpression in melanocytes accelerated melanoma formation, consistent with reprogramming to the NCP state and activation of super-enhancers that lead to melanoma. Our work highlights the importance of the reemergence of the NCP state as a barrier to melanoma initiation.
|
|
|
Overall design |
ChIP-seq analysis of histone 3 lysine 27 acetylation in human A375 melanoma cells treated with DMSO
|
|
|
Contributor(s) |
Kaufman CK, Yang S, Zhou Y, Zon LI |
Citation(s) |
26823433 |
Submission date |
Sep 28, 2014 |
Last update date |
May 15, 2019 |
Contact name |
Leonard Zon |
E-mail(s) |
zon@enders.tch.harvard.edu
|
Organization name |
Boston Children's Hospital
|
Department |
Oncology/Hematology
|
Street address |
1 Blackfan Circle
|
City |
Boston |
State/province |
MA |
ZIP/Postal code |
02115 |
Country |
USA |
|
|
Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
Samples (2) |
|
This SubSeries is part of SuperSeries: |
GSE75356 |
A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation |
|
Relations |
BioProject |
PRJNA262500 |
SRA |
SRP048200 |