Abstract
It is still unclear whether the sporadic form of dysplastic nevi (SDN) represents a premalignant lesion of malignant melanoma and whether genetic 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 from H and E-stained slide sections by using a modified microdissection technique and were screened for the presence of mutations and loss of heterozygosity (LOH) of p16(INK4a) and p53 genes using a polymerase chain reaction-based LOH, single-strand conformation polymorphism, and direct DNA sequencing analyses. Hemizygous deletion was detected in 9 of 12 informative cases (75%) for 9p21-22 (p16(INK4a)) at one or more loci and 60% (6/10) for 17p13 (p53). As for mutation, we found 3 missense mutations and 1 mutation in the first intron in p16(INK4a) and 2 missense 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 other skin cancers. This indicates that p16(INK4a) and p53 genetic alterations may play an important role in the evolution of SDN and may represent an early event in the develop ment of malignant melanoma. Furthermore, ultraviolet radiation might be the predominant etiologic agent in the development of SDN.
| Original language | English |
|---|---|
| Pages (from-to) | 667-672 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 237 |
| Issue number | 3 |
| DOIs | |
| State | Published - 28 Aug 1997 |
Bibliographical note
Funding Information:1This work was supported by the Catholic Medical Center Research Fund for special projects. 2To whom requests for reprints should be addressed. Fax: 822-637-6586. E-mail: gold®[email protected]. Abbreviations: SDN, sporadic form of dysplastic nevus; LOH, loss of heterozygosity; CMM, cutaneous malignant melanoma.
