Regular Article
Genetic Alterations ofp16INK4aandp53Genes in Sporadic Dysplastic Nevus,☆☆,

https://doi.org/10.1006/bbrc.1997.7212Get rights and content

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 whetherp16INK4aandp53genetic abnormalities could be associated with development of SDN, nevus cell nests were procured selectively from H & E-stained slide sections by using a modified microdissection technique and were screened for the presence of mutations and loss of heterozygosity (LOH) ofp16INK4aandp53genes 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 (p16INK4a) 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 inp16INK4aand 2 missense mutations inp53. Among these mutations inp16INK4aandp53,5 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 thatp16INK4aandp53genetic alterations may play an important role in the evolution of SDN and may represent an early event in the development of malignant melanoma. Furthermore, ultraviolet radiation might be the predominant etiologic agent in the development of SDN.

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    This work was supported by the Catholic Medical Center Research Fund for special projects.

    ☆☆

    Abbreviations: SDN, sporadic form of dysplastic nevusLOH, loss of heterozygosity; CMM, cutaneous malignant melanoma;

    A. B. Ackerman, Ed.

    2

    To whom requests for reprints should be addressed. Fax: 822-637-6586. E-mail: [email protected].

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