Developmental chromatin programs determine oncogenic competence in melanoma Journal Article


Authors: Baggiolini, A.; Callahan, S. J.; Montal, E.; Weiss, J. M.; Trieu, T.; Tagore, M. M.; Tischfield, S. E.; Walsh, R. M.; Suresh, S.; Fan, Y.; Campbell, N. R.; Perlee, S. C.; Saurat, N.; Hunter, M. V.; Simon-Vermot, T.; Huang, T. H.; Ma, Y.; Hollmann, T.; Tickoo, S. K.; Taylor, B. S.; Khurana, E.; Koche, R. P.; Studer, L.; White, R. M.
Article Title: Developmental chromatin programs determine oncogenic competence in melanoma
Abstract: Oncogenes only transform cells under certain cellular contexts, a phenomenon called oncogenic competence. Using a combination of a human pluripotent stem cell–derived cancer model along with zebrafish transgenesis, we demonstrate that the transforming ability of BRAFV600E along with additional mutations depends on the intrinsic transcriptional program present in the cell of origin. In both systems, melanocytes are less responsive to mutations, whereas both neural crest and melanoblast populations are readily transformed. Profiling reveals that progenitors have higher expression of chromatin-modifying enzymes such as ATAD2, a melanoma competence factor that forms a complex with SOX10 and allows for expression of downstream oncogenic and neural crest programs. These data suggest that oncogenic competence is mediated by regulation of developmental chromatin factors, which then allow for proper response to those oncogenes. © 2021 American Association for the Advancement of Science. All rights reserved.
Keywords: mutation; tumor; danio rerio; cell; cell component; cancer
Journal Title: Science
Volume: 373
Issue: 6559
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Date Published: 2021-09-03
Start Page: eabc1048
Language: English
DOI: 10.1126/science.abc1048
PROVIDER: scopus
PUBMED: 34516843
PMCID: PMC9440978
DOI/URL:
Notes: Article -- Export Date: 1 October 2021 -- Source: Scopus
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MSK Authors
  1. Satish K Tickoo
    483 Tickoo
  2. Lorenz Studer
    220 Studer
  3. Barry Stephen Taylor
    238 Taylor
  4. Richard Mark White
    68 White
  5. Travis Jason Hollmann
    126 Hollmann
  6. Richard Patrick Koche
    174 Koche
  7. Nathalie Gael Saurat
    6 Saurat
  8. Ryan Walsh
    8 Walsh
  9. Yujie Fan
    5 Fan
  10. Emily Dina Montal
    14 Montal
  11. Mohita Malay Tagore
    7 Tagore
  12. Miranda Victoria Hunter
    11 Hunter
  13. Ting-Hsiang Huang
    8 Huang
  14. Joshua Weiss
    14 Weiss
  15. Shruthy Suresh
    8 Suresh
  16. Sarah Catherine Perlee
    6 Perlee
  17. Yilun Ma
    9 Ma