GENETIC ALTERATIONS OF P16(INK4A) AND P53 GENES IN SPORADIC DYSPLASTIC NEVUS

It is still unclear whether the sporadic form of dysplastic nevi (SDN) represents a premalignant lesion of malignant melanoma and whether ge netic alterations are involved in the development of SDN. To determine whether p16(INK4a) and p53 genetic abnormalities could be associated with development of SDN, nevus cell nests were procured selectively fr om H & E-stained slide sections by using a modified microdissection te chnique and were screened for the presence of mutations and loss of he terozygosity (LOH) of p16(INK4a) and p53 genes using a polymerase chai n reaction-based LOH, single-strand conformation polymorphism, and dir ect DNA sequencing analyses. Hemizygous deletion was detected in 9 of 12 informative cases (75%) for 9p21-22 (p16(INK4a)) at one or more loc i and 60% (6/10) for 17p13 (p53). As for mutation, we found 3 missense mutations and 1 mutation in the first intron in pl6(INK4a) and 2 miss ense mutations in p53. Among these mutations in p16(INK4a) and p53, 5 of 6 mutations were of the C:G to T:A transitional type; this is known to be related to ultraviolet radiation as previously confirmed in oth er skin cancers. This indicates that pl6(INK4a) and p53 genetic altera tions may play an important role in the evolution of SDN and may repre sent an early event in the development of malignant melanoma. Furtherm ore, ultraviolet radiation might be the predominant etiologic agent in the development of SDN. (C) 1997 Academic Press.