Am J Pathol  1996 Sep;149(3):883-93 

Comment in:
 Am J Pathol. 1996 Sep;149(3):739-44.

Relevance of ultraviolet-induced N-ras oncogene point mutations in development
of primary human cutaneous melanoma.

van Elsas A, Zerp SF, van der Flier S, Kruse KM, Aarnoudse C, Hayward NK, Ruiter
DJ, Schrier PI.

Department of Clinical Oncology, University Hospital Leiden, The Netherlands.

Intermittent or recreational exposure to sunlight is thought to contribute to
development of human cutaneous melanoma. We investigated the incidence of ras
oncogene mutation in human cutaneous melanoma in connection to sun-exposed body
sites in the patient, using a large series of DNA samples derived from
paraffin-embedded material as well as from fresh tumor samples and cell lines.
We first show that, of the ras family, predominantly N-ras is activated (15%),
whereas rarely H-ras or K-ras are mutated. The occurrence of N-ras mutations
correlates with continuous exposure to sunlight of the primary tumor site. Of
all tumors initiated on chronically sun-exposed body sites, 26% contained
mutated N-ras, in contrast to 0% of sun-protected melanomas. Melanoma lesions
obtained from patients from North or Central Europe contained fewer N-ras
mutations (12%) as compared with patients from Australia (24%). Mutations were
specifically associated with nodular melanoma and to a lesser extent with
lentigo malignant melanoma. N-ras mutations did not correlate with metastasis or
survival parameters. This study identifies a subset of cutaneous melanomas that
contain in the primary lesion ultraviolet-induced N-ras mutations, which are
maintained through further progression.

PMID: 8780392 [PubMed - indexed for MEDLINE]