AI Article Synopsis
- - The "cancerized field" theory explains that in tissues with cancer-prone cells, only certain clones have the ability to start tumors, often involving oncogenic mutations like BRAF(V600E) found in benign nevi that usually do not progress to melanoma.
- - Research using transgenic zebrafish shows that a single abnormal melanocyte can switch back to an embryonic neural crest progenitor state, which is critical for the onset of melanoma in a specific genetic context (BRAF(V600E) mutation combined with p53 deficiency).
- - The transcription factor sox10 is implicated in this process, as its overexpression speeds up melanoma development by activating genes related to the neural crest state, signaling that the re
Article Abstract
The "cancerized field" concept posits that cancer-prone cells in a given tissue share an oncogenic mutation, but only discreet clones within the field initiate tumors. Most benign nevi carry oncogenic BRAF(V600E) mutations but rarely become melanoma. The zebrafish crestin gene is expressed embryonically in neural crest progenitors (NCPs) and specifically reexpressed in melanoma. Live imaging of transgenic zebrafish crestin reporters shows that within a cancerized field (BRAF(V600E)-mutant; p53-deficient), a single melanocyte reactivates the NCP state, revealing a fate change at melanoma initiation in this model. NCP transcription factors, including sox10, regulate crestin expression. Forced sox10 overexpression in melanocytes accelerated melanoma formation, which is consistent with activation of NCP genes and super-enhancers leading to melanoma. Our work highlights NCP state reemergence as a key event in melanoma initiation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868069 | PMC |
| http://dx.doi.org/10.1126/science.aad2197 | DOI Listing |
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