Though multiple genetic alterations are associated with melanoma development, scientists have not been able to establish a direct causal link between these alterations and human cancer growth. Determining whether these mutations have the potential themselves to induce cancer or simply play a supporting role also has been difficult.
To determine the impact of genetic alterations associated with human melanoma, Yakov Chudnovsky; his advisor, Paul Khavari; postdoctoral fellow Amy Adams, and colleagues generated human skin tissue containing cells selectively engineered to express specific mutations found in melanoma. They report their findings in the June 12, 2005, issue of the journal Nature Genetics, offering clues to the oncogenic potency of several genes implicated in the development of melanoma.
Melanoma is the deadliest form of skin cancer, resulting from the malignant transformation of cells called melanocytes. Over the past four decades, the incidence of melanoma has risen 15-fold, a more rapid increase than that of any other cancer.
"The only current treatment is early detection and excision," Chudnovsky said. "But no treatment can substantially enhance patient survival once metastasis has occurred."
To simulate the environment in which melanoma naturally arises, the research team introduced one or more cancer-associated genes into human melanocytes, the pigment-producing cells that normally reside in the deepest layer of the skin. The genetically engineered melanocytes were then combined with keratinocytes, the cells that give skin its structure, to form a sample of human skin that was grafted onto laboratory mice. The mice were observed for