Science: The same mutation occurs. Why do some cells form tumors?

Although specific DNA mutations can cause tumors, they do not promote transformation in all cellular contexts

Baggiolini et al.

Cells that are prone to tumor formation show higher levels of chromatin-modifying factors, such as ATAD2 protein

Structured abstract

Tumor analysis shows that DNA mutations can transform cells in some cases

principle

During development, neural crest cells produce melanocytes, which then further differentiate into melanocytes

result

We modified the zebrafish to use the sox10 promoter, mitfa promoter or tyrp1 promoter to drive the expression of BRAFV600E under the background of p53-/-

To extend these results to human cells, we developed a tumor model derived from human pluripotent stem cells (hPSC)

Performing RNA sequencing on these cells (with or without BRAFV600E), we found that neural crest cells and melanocytes have a strong transcriptional response to oncogenes, and although the activation of phosphorylated extracellular signal-regulated kinase (pERK) is the same, But melanocytes hardly changed

Pathway analysis showed that several chromatin-modifying enzymes, including readers, writers, and erasers (ATAD2, BPTF, BAZ1A, EZH2, etc.

In vitro, expression of ATAD2 in hPSC-derived melanocytes formed a phenotype more like progenitor cells, and inhibition of ATAD2 impaired neural crest differentiation

in conclusion

Overall, these data indicate that carcinogenicity is mediated by oncogenes (such as BRAFV600E), lineage-specific transcription factors (such as SOX10), and chromatin modifiers (such as ATAD2) that regulate development

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Developmental chromatin programs determine oncogenic competence in melanoma

SCIENCE 3 Sep 2021 Vol 373, Issue 6559

DOI: 10.