Rare Genetic Disorder Reveals How UV Exposure May Cause Melanoma Jim Breitfeller

March 24, 2009 • Volume 6 / Number 6
NCI Cancer Bulletin

Much of what is known about how ultraviolet radiation (UV) causes skin cancer relates only to basal cell and squamous cell carcinoma. For melanoma, a less common but far more deadly form of the disease, there has been less evidence. New research suggests that UV-induced mutations in a gene called PTEN that normally suppresses tumors may play an important role in the formation of melanoma, according to findings published yesterday in the Proceedings of the National Academy of Sciences.

Researchers from NCI’s Center for Cancer Research and their collaborators at Brown University analyzed 59 melanoma samples taken from 8 patients with xeroderma pigmentosum (XP) who were seen at the NIH Clinical Center between 1971 and 2008. XP is a rare genetic disorder that compromises the ability of cells to repair DNA damage to the skin, putting these patients at a nearly 1,000-fold increased risk of melanoma, which progresses rapidly.

The researchers found that 56 percent of the XP melanomas analyzed harbored mutations in the PTEN gene. Of these mutations, 91 percent included DNA base substitutions of the type that usually result from UV damage, with between 1 and 4 changes per tumor. These mutations were also detected among melanomas in situ, those at the earliest stage of disease. Melanomas from the same person sometimes had different PTEN mutations, indicating that they arose independently.

The findings “provide a clear mechanistic framework for the role of UV in the induction of melanomas,” Dr. Kenneth Kraemer and colleagues wrote, “and a sound rationale for UV protective measures for melanoma prevention.”

source: http://www.cancer.gov/ncicancerbulletin/032409/page3#d

NCI Cancer Bulletin 3-24-2009


Take care

Jimmy B