How moles change into melanoma

Date:
November 23, 2021
Source:
Huntsman Cancer Institute
Summary:
Melanoma researchers published a study that gives a new explanation
of what causes moles to change into melanoma. These findings pave
the way for more research into how to reduce the risk of melanoma,
delay development, and detect melanoma early.



FULL STORY ========================================================================== Moles and melanomas are both skin tumors that come from the same cell
called melanocytes. The difference is that moles are usually harmless,
while melanomas are cancerous and often deadly without treatment. In
a study published today in eLife Magazine, Robert Judson-Torres, PhD,
Huntsman Cancer Institute (HCI) researcher and University of Utah (U of U) assistant professor of dermatology and oncological sciences, explains how common moles and melanomas form and why moles can 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, called
BRAF gene mutations, are found in over 75% of moles. The same change
is also found in 50% of melanomas and is common in cancers like colon
and lung. It was thought that when melanocytes only have the BRAFV600E
mutation the cell stops dividing, resulting in a mole. When melanocytes
have other mutations with BRAFV600E, they divide uncontrollably, turning
into melanoma. This model is called "oncogene- induced senescence."
"A number of studies have challenged this model in recent years,"
says Judson- Torres. "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." With help from collaborators across HCI
and the University of California San Francisco, the study team took moles
and melanomas donated by patients and used transcriptomic profiling and
digital holographic cytometry. 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," says Judson-Torres.

The study shows melanocytes that turn into melanoma do not need to
have additional mutations but are actually affected by environmental
signaling, when cells receive signals from the environment in the skin
around them that give them direction. 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," says 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 doctors 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, and to detect melanoma early.

The study was funded by National Institutes of Health/National Cancer
Institute including P30 CA042014, 5 For The Fight, and Huntsman Cancer Foundation.

Judson-Torres recognizes critical contributions by other HCI scientists, including Rachel Belote, PhD; Sheri Holmen, PhD; Matthew VanBrocklin, PhD; David Lum, PhD; Doug Grossman, MD, PhD; and University of California San Francisco scientists Andrew McNeal, PhD; Maria Wei, MD, PhD; and Ursula
Lang, MD, PhD.

========================================================================== Story Source: Materials provided by Huntsman_Cancer_Institute. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Andrew S McNeal, Rachel L Belote, Hanlin Zeng, Marcus Urquijo,
Kendra
Barker, Rodrigo Torres, Meghan Curtin, A Hunter Shain, Robert HI
Andtbacka, Sheri Holmen, David H Lum, Timothy H McCalmont, Matt W
VanBrocklin, Douglas Grossman, Maria L Wei, Ursula E Lang, Robert
L Judson-Torres. BRAFV600E induces reversible mitotic arrest in
human melanocytes via microrna-mediated suppression of AURKB. eLife,
2021; 10 DOI: 10.7554/eLife.70385 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211123162809.htm

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