When melanocyte stem cells accumulate a sufficient number of genetic mutations, they can become the cells where melanomas originate, Cornell University researchers report.

Under normal conditions, ultraviolet (UV) radiation from the sun activates melanocytes to release melanin, but if melanocyte stem cells have surpassed a threshold of genetic mutations, a tumor can start to grow when those skin stem cells are activated by sun exposure.

“If you had mutations that were sufficient for melanoma, everything would be fine until you went out and got a sunburn,” says Andrew White, assistant professor of biomedical sciences at Cornell’s College of Veterinary Medicine, and senior author of a study published this month in the journal Cell Stem Cell, in a news release.

 “The stimuli that would normally just give you a tanning response could in fact start a melanoma instead,” White said.

The researchers also may have discovered a way to prevent melanomas caused by mutated stem cells. A gene called Hgma2 was suspected to become expressed in the skin under UV radiation. When expressed, Hgma2 facilitates melanocyte stem cells to move from the base of skin hair follicles to the skin’s surface, where the cells release melanin. The research team used mice engineered with melanocyte stem cell mutations. One set of mice had the mutations, while another set with the mutations had the Hgma2 gene deleted. They then gave the mice a very low dose of UV radiation, just enough to trigger a tanning response. Mice with tumor-causing mutations and the Hgma2 gene intact developed melanomas, but the mice with mutations and the deleted gene remained healthy.

More study is needed to better understand the Hgma2 gene’s function.

“We have an actual mechanism, with Hgma2, that can be explored in the future and could be a way we can prevent melanomas from happening,” White said.

The study was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Cancer Research Program, the Cornell Center for Vertebrate Genomics, the Cornell Stem Cell Program and the National Institutes of Health.

CAPTION: University
Fluorescence microscopy reveals melanoma (red, left; black, right) emerging from melanocyte stem cells.

PHOTO CREDIT: Hyeongsun Moon and Andrew White, Cornell PHOTO