Emerging from the Field

The concept of field cancerization is well established, especially in skin. Essentially, fields of skin damage related usually to ultraviolet (UV) exposure have acquired DNA damage that primes them for cancer development. However, it is unclear why, given the swath of UV-damaged tissue, clones that give rise to cancer remain dramatically rare.

These researchers used a model of melanoma in which oncogenic BRAF^V600E is expressed in melanocytes in zebrafish that lack P53. An additional twist here is that the protein crestin was linked to a green fluorescent protein, enabling all crestin-expressing cells to be visualized in vivo. Incredibly, rare clones of BRAF^V600E-expressing melanocytes turned on crestin expression, thus re-expressing a neural crest program. By observing the animals across their development, they saw that crestin expression was confined to the embryo during neural crest development and then shut off, only to re-emerge in melanomas.

They then tracked down pieces of DNA that appeared to regulate crestin in this fashion, showing that SOX10 and PAX3 were important regulators of crestin expression. Indeed, removal of SOX10 delayed melanoma formation. Finally, by tracing transcriptional patterns regulated by histone modifications across the genome, they identified similarities in large-scale transcriptional drivers suggesting a close correspondence between human melanoma cell lines and neural crest progenitors.