Ultraviolet light-inducible mutations very common with hereditary melanomas

Nearly all patients with a type of hereditary melanoma have ultraviolet light (UV)-inducible mutations in the NRAS proto-oncogene, according to a report published in the June 4th issue of the Journal of the National Cancer Institute.

Acquired mutations in NRAS have been implicated in the development of melanoma. However, it was unclear how often such mutations occur in patients with hereditary melanomas related to a germline mutation in the tumor suppressor, cyclin-dependent kinase inhibitor 2A (CDKN2A).To investigate, Dr. Johan Hansson and colleagues, from Karolinska Hospital in Stockholm, analyzed the NRAS gene in 39 biopsy samples from patients with CDKN2A germline mutations and in 10 samples from patients with sporadic melanomas. The authors found that 95% of primary hereditary melanomas contained activating NRAS mutations. In contrast, only 10% of the sporadic melanomas harbored such mutations (p < 0.001).In nine patients with primary hereditary melanomas, the researchers identified multiple activating NRAS mutations. In addition, NRAS mutations were detected in samples containing premalignant lesions, such as dysplastic nevi."This is the first report, to our knowledge, that documents a high frequency of NRAS mutations in primary melanomas in members of melanoma-prone families who also have known germline CDKN2A mutations," Dr. Hansson's team states."Our results support the concept of cooperation between CDKN2A inactivation and ras activation in the pathogenesis of human cutaneous melanoma," they conclude.(Source: J Natl Cancer Inst 2003;95:790-798: Reuters Health: June 6, 2003: Oncolink)