Moles Can Become Melanomas Through Nongenetic Transitions, UC Irvine Study Shows

Hui Xiao, PhD, and a team of scientists led by skin cancer specialist Anand Ganesan, MD, PhD, left, discovered precursor stem cells that can become melanomas through nongenetic pathways, a finding that could help early detection of the aggressive skin cancer.

Irvine, Calif., June 26, 2025 — Researchers at the University of California, Irvine exploring the genesis of melanoma have identified a cell type in animal and human models that can initiate tumors in the absence of other genetic mutations.

These cells, which resemble neural crest stem cells, were found to be present in human and mouse melanomas, as well as in normal skin, the researchers report in a study published today in the journal Nature Communications. Single-cell transcriptomics and advanced bioinformatics approaches revealed that these cells could act as “precursors of malignant cells,” a finding that has significant implications for developing strategies to detect melanoma early or even prevent melanoma from forming. 

“We show that an initial mutation, known to generate either a normal mole or a tumor, need not be followed by a second mutation to change into a melanoma tumor,” said Anand Ganesan, MD, PhD, a UC Irvine professor of dermatology and biological chemistry and corresponding author of the study.

“This opens up the possibility of reverting the tumor cell to back into a normal cell if indeed the event that is causing it is not permanent, like a mutation," added the UCI Health dermatologist and skin cancer specialist. "It also opens up the possibility that one could design a therapy to stop this cellular transition as a way to prevent melanoma.”

Melanoma, which is expected to cause more than 8,000 U.S. deaths in 2025, is a type of cancer that arises in the skin’s pigment-making cells. Called melanocytes, these cells can form a pigmented lesion on the skin called a “mole” and also known as a nevus. Most moles are benign, but those that become melanomas can spread rapidly to other organs throughout the body.

Read the full press release in UCI Health.