Short answers, pulled from the story.
Melanoma is primarily caused by DNA damage from ultraviolet radiation, either from sunlight or tanning devices. UV light triggers mutations in skin cell DNA, most commonly cytosine to thymine transitions, that can disrupt tumor suppressor genes and oncogenes. Genetic factors, including mutations in CDKN2A and BRAF, and a weakened immune system also contribute.
Early signs include changes to existing moles summarized by the ABCDE mnemonic: Asymmetry, irregular Borders, variegated Color, Diameter greater than 6 mm (about the size of a pencil eraser), and Evolution over time. Nodular melanoma has separate signs: it is elevated above the skin surface, firm to the touch, and growing.
In the United States, the five-year survival rate for localized melanoma is 100 percent. When melanoma has spread to regional lymph nodes, the five-year survival rate is 76 percent. For distant metastatic melanoma, the five-year survival rate was 34.6 percent among people diagnosed between 2015 and 2021.
Australia has the highest melanoma incidence in the world because people of European descent settled a country with intense direct sunlight to which their skin was not adapted. As of 2008, age-standardized incidence rates in Australia were at least 12 times higher than the world average. Australian melanoma incidence increased by more than 30 percent between 1991 and 2009.
The most frequent mutation occurs at the 600th codon of the BRAF gene, present in approximately 50 percent of melanoma cases. RAS gene mutations occur in about 30 percent of cases. BRAF V600E or V600K mutations make melanoma more responsive to the approved combination of dabrafenib plus trametinib, which improved progression-free survival from 9 percent to 41 percent in trials.
Ipilimumab was approved by the FDA in March 2011 for late-stage melanoma that has spread or cannot be surgically removed. In clinical trials, it increased median survival from 6.4 to 10 months compared to an experimental vaccine. A course of treatment costs $120,000 and the drug is sold under the brand name Yervoy.