Moles and melanomas both originate from the same type of cell—melanocytes. A study published by McNeal et al in eLife Magazine aimed to explain how common moles and melanomas form and why moles can subsequently change into melanoma.
Melanocytes are cells that give color to the skin to protect it from the sun’s rays. Specific changes to the DNA sequence of melanocytes—BRAF gene mutations—are found in over 75% of moles. The same change is also found in 50% of melanomas and is common in other cancer types, like colon and lung cancers. It was thought that when melanocytes only have a BRAF V600E mutation, the cell stops dividing, resulting in a mole. When melanocytes have other mutations with BRAF V600E, they divide uncontrollably, turning into melanoma. This model is called “oncogene-induced senescence.”
“A number of studies have challenged this model in recent years,” said study coauthor Robert Judson-Torres, PhD, Huntsman Cancer Institute researcher and Assistant Professor of Dermatology and Oncological Sciences at the University of Utah. “These studies have provided excellent data to suggest that the oncogene-induced senescence model does not explain mole formation, but what they have all lacked is an alternative explanation—which has remained elusive.”
Current Study Findings
The study team took moles and melanomas donated by patients and performed transcriptomic profiling and digital holographic cytometry on the samples. Transcriptomic profiling lets researchers determine molecular differences between moles and melanomas; digital holographic cytometry helps researchers track changes in human cells.
“We discovered a new molecular mechanism that explains how moles form, how melanomas form, and why moles sometimes become melanomas,” said Dr. Judson-Torres.
The study showed that melanocytes that turn into melanoma do not need to have additional mutations, but are actually affected by environmental signaling. Melanocytes express genes in different environments, telling them to either divide uncontrollably or stop dividing altogether.
“Origins of melanoma being dependent on environmental signals gives a new outlook in prevention and treatment,” said Dr. Judson-Torres. “It also plays a role in trying to combat melanoma by preventing and targeting genetic mutations. We might also be able to combat melanoma by changing the environment.”
These findings create a foundation for researching potential melanoma biomarkers, allowing physicians to detect cancerous changes in the blood at earlier stages. The researchers are also interested in using these data to better understand potential topical agents to reduce the risk of melanoma, delay development, or stop recurrence, as well as to detect melanoma early.
Disclosure: The study was funded by National Institutes of Health/National Cancer Institute, 5 For The Fight, and Huntsman Cancer Foundation. For full disclosures of the study authors, visit elifesciences.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.