Researchers fromUniversity of Utah (U of U) Huntsman Cancer Institute (HCI) they generated the first “atlas”Of human melanocytes located throughout the body. By further analyzing the data from the Atlas, the researchers found that there are several types of melanocytes, including what appears to be the cell of origin of the acral melanoma, a subtype of melanoma that mainly affects people of color. Researchers predict that these findings will lead to more targeted treatments for melanoma.
The results of the study were published today in the magazine Nature Cell Biology .
Here’s what the new studies on acral melanoma say
Melanoma, the deadliest form of skin cancer, originates in melanocytes, the cells that color the skin and protect it from sunlight. Melanocytes were thought to be interchangeable, but the lead author Rachel Belote, Ph.D., HCI postdoctoral fellow in the Judson-Torres Lab, says: “I have noticed that not all melanocytes respond to signals from surrounding cells in the same way. If melanocytes from the same piece of skin respond differently to the same stimuli, this would mean that there are actually different types of melanocytes ”.
The research team has begun to look more deeply into human melanocytes. They examined melanocytes through different stages of development, aging, anatomical locations, sexes and skin tones. While most studies have used melanocytes similar only to human ones, here the focus has remained entirely on human melanocytes. Together, the researchers generated the first atlas, or map, of melanocytes throughout the human body and through the stages of cell development.
“We also focused on solving a single cell, studying the cells one at a time. It was the combination of many of these variables, in particular the study of the stages of human development in different anatomical positions with the resolution of a single cell, that allowed us to make the discoveries we made. “, Says the mentor of Belote and senior author of the study, Robert Judson-Torres, Ph.D., HCI researcher and assistant professor of dermatology and oncology sciences U of U.
One such discovery was a new melanocyte which appears to be the cell of origin of a specific melanoma subtype called acral melanoma.. There are very few treatment options for this type of melanoma, which is the most common type in people with darker skin.
“This study really confirms that acral melanoma is a thing in itself”, says Judson-Torres. “Most of the history of the exploration of acral melanoma has treated it as an afterthought of the more common subtypes of melanoma that predominantly affect the white population “. Judson-Torres says the classic approach has been to find treatments for the most common disease first, then see if treatment works on acral melanoma.
“This approach has not been particularly successful. We expect this study to change the way acral melanoma is approached and studied, and we hope it will quickly lead to specific therapies for acral.“, he claims.
The study also revealed three other findings. The team has scovered specific genes associated with changes in skin tones in a single person, not related to sun exposure. The team identified genes that mark progressing melanomas that are less likely to respond to treatments. The team also discovered the genes that make human melanocytes unique.
“We have confirmed that there are different types of melanocytes that are not only associated with different biological characteristics corresponding to specific regions of the skin, but also give rise to different types of melanoma “, Belote says.
Researchers are planning follow-up research, including the development of specific in vivo and in vitro models for acral melanoma to begin screening for specific therapies for acral melanoma.
Differences between acral melanoma and acral nevi
Melanocytic nevi, or moles, are non-malignant growths that arise from skin cells that produce pigments. They are found mainly in areas exposed to the sun; however, they can also be found in sun-protected areas, such as palms, soles of the feet, and nail beds, where they are known as acral nevi. While the mutation profile of nevi in sun-exposed areas is well understood, less is known about genes that are commonly mutated in acral nevi. And while a subset of sun-exposed skin melanoma occurs in nevi, the link between nevi and melanoma in acral skin is poorly understood.
Melanoma is one of the most common types of cancer, with an estimated 100,000 new cases diagnosed in 2020 in the United States. Acral melanoma is a subtype on areas of the skin not exposed to the sun and is not linked to exposure to ultraviolet radiation. Although both conditions arise from pigment-producing melanocytes, melanoma and acral melanoma differ in several ways. Patients with acral melanoma tend to have a poorer response to treatment and a higher mortality rate than patients with typical melanoma. Furthermore, the two types of melanoma differ in their mutation profile.
About 30% of malignant nelanomas result from non-malignant melanocytic nevi. One of the most common genetic alterations in melanocyte nevi, as well as melanoma, are mutations in the BRAF gene.
To determine if there is a genetic link between acral nevi and acral melanoma, Moffitt researchers performed a phenetic analysis on 50 acral nevi of 49 patients, 19 males and 30 females. They found that, unlike acral melanoma, activating mutations in the BRAF gene were very common in nevi, with 86% of patients having a mutation in the BRAF gene. Additionally, 10% of patients had activating mutations in the NRAS gene, which were mutually exclusive from BRAF mutations.
These observations demonstrate that acral nevi and acral melanoma have different mutation patterns. “Acral nevi demonstrated a mutational spectrum very similar to that of nevi on sun-exposed skin, suggesting that acral nevi is unlikely to be the precursor lesion for most acral melanomas”, he has declared Keiran Smalley, Ph.D., study author and director by Donald A. Adam Melanoma and the Skin Cancer Center of Excellence in Moffitt. “We hope our findings lead to a better understanding of how acral melanoma develops. ”
“This is the largest series of acral nevi that have been sequenced to date, and the results have been amazing to me.“, he said Jane Messina, MD, senior author of the study and senior member of the Department of Skin Oncology. “Furthermore, most of our patients were of white / European origin, while previous studies were mostly conducted on Asian populations where there is a much higher frequency of snows acrali. The frequent presence of a mutation with a strong link to sun exposure suggests that even acral skin can be prone to sun damage. “
In Italy, cases of melanoma have undergone a 20% increase, from 12,300 in 2019 to almost 14,900 in 2020: “On the one hand, the availability of better tools for diagnosis and greater participation of citizens in awareness campaigns for the control of moles. On the other hand, the consequences in adults of incorrect exposure to the sun as adolescents and the use of sun lamps, inserted by the International Agency for Research on Cancer (IARC) in the category of maximum risk of carcinogenic substances, are increasingly observed, at equal to cigarette smoke “ it was to declare it Paola Queirolo, Director of the Melanoma, Sarcoma and Rare Tumors Division at the European Institute of Oncology in Milan.
“In our country, melanoma is the second most frequent cancer in men under 50 and the third in women in that age group. The risk of onset is linked to genetic, phenotypic and environmental factors. The most important is identified in the exposure to UV rays, in relation to the absorbed doses, the type of exposure (intermittent rather than chronic) and age (children and adolescents at greater risk). The estimated increase this year is in line with the trend we have been observing for some time “, continued the scientist.
“In the period 2008-2016, in fact, melanomas were the cancers that recorded the greatest average annual increase, both in men (+ 8.8% in total, + 9.1% in over 70s) and in women (+7 , 1% in total, + 7.6% in under 50s) and in all age groups. This is a very sustained growth which, although it reflects voluntary exposure to UV rays that began in recent decades and the recent availability of increasingly accurate diagnostic techniques, indicates the need to implement timely primary prevention interventions, precisely to reverse this worrying trend in the coming years”.
“The rules to follow are simple: you must not expose yourself to the sun in the central hours of the day, the protective cream must always be applied and sun lamps must be absolutely avoided. And every year it is necessary to undergo the control of moles by the dermatologist “, concluded the expert.