A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation
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[superscript V600E] mutations but rarely become melanoma. The zebrafish crestin gene is express...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
| Published: |
American Association for the Advancement of Science (AAAS)
2016
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| Online Access: | http://hdl.handle.net/1721.1/105872 https://orcid.org/0000-0001-8855-8647 |
| _version_ | 1826195199431278592 |
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| author | Kaufman, C. K. Mosimann, C. Yang, S. Thomas, A. J. Ablain, J. Tan, J. L. Fogley, R. D. van Rooijen, E. Hagedorn, E. J. Ciarlo, C. White, R. M. Matos, D. A. Puller, A.-C. Santoriello, C. Liao, E. C. Zon, L. I. Fan, Zi Peng Young, Richard A. |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Kaufman, C. K. Mosimann, C. Yang, S. Thomas, A. J. Ablain, J. Tan, J. L. Fogley, R. D. van Rooijen, E. Hagedorn, E. J. Ciarlo, C. White, R. M. Matos, D. A. Puller, A.-C. Santoriello, C. Liao, E. C. Zon, L. I. Fan, Zi Peng Young, Richard A. |
| author_sort | Kaufman, C. K. |
| collection | MIT |
| description | 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[superscript 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[superscript 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. |
| first_indexed | 2024-09-23T10:08:58Z |
| format | Article |
| id | mit-1721.1/105872 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:08:58Z |
| publishDate | 2016 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1058722022-09-30T19:12:22Z A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation Kaufman, C. K. Mosimann, C. Yang, S. Thomas, A. J. Ablain, J. Tan, J. L. Fogley, R. D. van Rooijen, E. Hagedorn, E. J. Ciarlo, C. White, R. M. Matos, D. A. Puller, A.-C. Santoriello, C. Liao, E. C. Zon, L. I. Fan, Zi Peng Young, Richard A. Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Young, Richard A Fan, Zi Peng 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[superscript 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[superscript 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. 2016-12-19T16:29:02Z 2016-12-19T16:29:02Z 2016-01 2015-08 Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/105872 Kaufman, C. K. et al. “A Zebrafish Melanoma Model Reveals Emergence of Neural Crest Identity during Melanoma Initiation.” Science 351.6272 (2016): aad2197-aad2197. https://orcid.org/0000-0001-8855-8647 en_US http://dx.doi.org/10.1126/science.aad2197 Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Kaufman, C. K. Mosimann, C. Yang, S. Thomas, A. J. Ablain, J. Tan, J. L. Fogley, R. D. van Rooijen, E. Hagedorn, E. J. Ciarlo, C. White, R. M. Matos, D. A. Puller, A.-C. Santoriello, C. Liao, E. C. Zon, L. I. Fan, Zi Peng Young, Richard A. A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation |
| title | A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation |
| title_full | A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation |
| title_fullStr | A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation |
| title_full_unstemmed | A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation |
| title_short | A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation |
| title_sort | zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation |
| url | http://hdl.handle.net/1721.1/105872 https://orcid.org/0000-0001-8855-8647 |
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