Frequency of UV-Inducible NRAS Mutations in Melanomas of Patients With Germline CDKN2A Mutations

摘要: Background: Germline alterations in cyclin-dependent kinase inhibitor 2A (CDKN2A) are important genetic factors familial predisposition to melanoma. Activating mutations of the NRAS proto-oncogene among most common somatic cutaneous malignant melanomas. We investigated occurrence melanomas and dysplastic nevi individuals with germline CDKN2A mutations. Methods: Genomic DNA was extracted from 39 biopsy samples (including primary melanomas, metastatic nevi) 25 patients six Swedish families a hereditary melanoma who carried also 10 sporadic analyzed using polymerase chain reaction, single-strand conformation polymorphism analysis, nucleotide sequence analysis. Differences mutation frequency between were by chi-square test. All statistical tests two-sided. Results: codon 61, all which either CAA(Gln)-AAA(Lys) or CAA(Gln)-CGA(Arg) mutations, found 95% (20/21) but only 10% (1/10) (P<.001). Multiple activating detected tumor cells different regions individual nine patients. that these retained their metastases. at sites other than 61 present indicating instability this locus. an situ melanoma, suggesting role for such during early development. Conclusions: The high may be result hypermutability phenotype associated development