Scientists Finally Discovered Missing Piece of How Melanoma Becomes Immortal

Jonathan Alder, Ph.D., and his team at the University of Pittsburgh School of Medicine have discovered the missing puzzle piece of how melanoma strives to become immortal. Medical Xpress reports that the team described the perfect combination of genetic alterations tumors use to promote explosive growth and prevent death, helping scientists better understand and treat melanoma.

Alder, an assistant professor at the Division of Pulmonary, Allergy, and Critical Care Medicine at the university's School of Medicine said that they used a method based on previous basic research and connected it to something that happens to patients.

(Photo: American Cancer Society/Getty Images)
Detail of a person with malignant melanoma, a malignant skin tumor involving the skin cells that produce pigment.

Cancer Uses Mutated Telomeres to Stay Alive

Telomeres are protected caps at the end of chromosomes that are required to prevent DNA from degrading. They become shorter in each replication in healthy cells until they become so short that the cell can no longer divide.

If maintenance of telomere length is disrupted, it may result in severe diseases. Short telomeres lead to premature aging and death, but long ones can cause cancer. Scientists observed that many cancer types, like melanoma, have strikingly long telomeres.

Telomerase protein is responsible for elongating telomeres and protecting them from damage to prevent cell death. But the protein is inactive in most cells, so some cancer cells use the telomerase gene called TERT to activate it and allow cells to continue growing.

According to their press release, about 75% of melanoma tumors have mutations in the TERT gene that stimulate the production of telomerase and increase its activity. But the team noticed that mutated TERT in melanocytes was just half the story. The team was determined to find this missing link and found that mutations in a telomere-binding protein called TPP1 were similar to TERT and activated the production of the protein.

When Chun-on added mutated TERT and TPP! back to the healthy cells, the two proteins synergized and created long telomeres seen in melanocytes. The team concludes that the missing puzzle piece in how melanoma controls their immortality is in TPP1, which was hiding in plain sight.

The discovery changed the way scientists understand melanoma's onset, which opened new ways to improve treatment by identifying a telomere maintenance system unique to a cancer type. Their study, titled "TPP1 promoter mutations cooperate with TERT promoter mutations to lengthen telomeres in melanoma," was published in Science.

What is Melanoma?

According to Cleveland Clinic, melanoma is the most dangerous type of skin cancer that can grow quickly and spread to any organ. It comes from skin cells called melanocytes that produce melanin or the dark pigment that gives skin its color.

About 30% of melanoma cases started with existing moles, while the rest started in normal skin. That is why experts recommend paying attention to changes in the skin because it could signal the start of skin cancer.

To spot any signs, use the American Academy of Dermatology's "ABCDE" memory device. Letter A stands for "Asymmetry," B for "Border," C for "Color," D for "Diameter," and E for "Evolving."

Although some types of melanoma do not fit the ABCDE rule, it is best to consult a doctor for any unusual bumps, rashes, or skin changes that seem not to go away. The other way is through the ugly duckling sign. If one of the moles looks different from others, it is the ugly duckling and should be checked by dermatologists.

Since it can grow and spread quickly, a delay in treating melanomas may mean the difference between life and death. Knowing one's risk will help people become extra vigilant in watching changes in their skin.