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skin cancer

With these gene mutations, a tan sets off melanoma

New research sheds light on the beginnings of melanoma in the body—and potentially how to stop it from starting.

Melanoma, a cancer of skin pigment cells called melanocytes, will strike an estimated 87,110 people in the United States in 2017, according to the Centers for Disease Control and Prevention. A fraction of those melanomas come from pre-existing moles, but the majority of them come from sources unknown—until now.

“If you had mutations that were sufficient for melanoma, everything would be fine until you went out and got a sunburn…”

In a new study, researchers found that when melanocyte stem cells accumulate a sufficient number of genetic mutations, they can become the cells where these cancers originate.

Under normal conditions, ultraviolet (UV) radiation from the sun activates melanocytes to release melanin, a pigment that protects the skin from the sun’s rays. 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, an assistant professor of biomedical sciences at Cornell University’s College of Veterinary Medicine, and senior author of the study.

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

Virus sleeps for years then wakes up to cause skin cancer

The researchers may have also discovered a way to prevent melanomas caused by mutated stem cells. The researchers suspected a gene called Hgma2 would be 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 (the epidermis), where the cells release melanin.

The researchers used mice engineered with melanocyte stem cell mutations in the study. 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.

Researchers must do more work 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 says.

Tool detects melanoma cells that don’t look ‘regular’

The researchers report their work in the journal Cell Stem Cell.

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 University Stem Cell Program, and the National Institutes of Health supported the study.

Source: Cornell University

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