Genetic Alterations ofp16INK4aandp53Genes in Sporadic Dysplastic Nevus

doi:10.1006/bbrc.1997.7212

Biochemical and Biophysical Research Communications

Volume 237, Issue 3, 28 August 1997, Pages 667-672

https://doi.org/10.1006/bbrc.1997.7212 Get 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 whetherp16^INK4aandp53genetic 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) ofp16^INK4aandp53genes 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 inp16^INK4aand 2 missense mutations inp53. Among these mutations inp16^INK4aandp53,5 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 thatp16^INK4aandp53genetic 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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dysplastic nevi (DN) share some clinical and histological features with melanoma and have been considered intermediate lesions toward malignant transformation. However, scientific evidence of DN representing melanoma precursors is still incomplete, and many observations pointed toward their being a distinct biological entity. The current definition of DN is also confusing and the practical consequence of this uncertainty is the excessive excision of DN with severe atypia. MicroRNAs (miRNAs) are small RNAs that regulate gene expression and whose global expression can classify normal and pathological tissues.
given these considerations, we decided to perform a small RNA profiling study in a group of DN and invasive melanomas obtained from the same patient, to assess tumor evolution according to the global microRNA expression.
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Favorable long-term outcomes in patients with histologically dysplastic nevi that approach a specimen border
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Patients with multiple clinically dysplastic nevi are at increased risk for development of melanoma. However, the risk of melanoma arising in a histologically dysplastic nevus (HDN) is unknown.
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We performed a retrospective study of patients evaluated in our dermatology department from January 1, 1980, to December 31, 1989, who had a HDN that extended to within 0.2 mm of a microscopic punch, shave, or excision border and was not re-excised.
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Dysplastic Nevi
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Citation Excerpt :
Silencing of p16 with mutations at both alleles was found in many of the melanomas in this study but in none of the nevi, indicating that loss of heterozygosity may be required for tumorigenesis. Others have also demonstrated point mutations in p16 and also in p53 in addition to hemizygous p16 deletions in dysplastic nevi from patients with no known family history of dysplastic nevus syndrome.66 Several researchers have examined possible explanations for increased genetic mutations in patients with dysplastic nevi.
The dysplastic nevus: From historical perspective to management in the modern era: Part II. Molecular aspects and clinical management
2012, Journal of the American Academy of Dermatology
Citation Excerpt :
Several studies have investigated the presence of p53 mutations in DN. Lee et al32 found two p53 missense mutations in 12 DN examined. In another study, Levin et al35 detected p53 mutations in two of five DN and 2 of 11 CN.
The dysplastic nevus is a discreet histologic entity that exhibits some clinical and histologic features overlapping with common nevi and melanoma. These overlapping features present a therapeutic challenge, and with a lack of accepted guidelines, the management of dysplastic nevi remains a controversial subject. Although some differences between dysplastic and common nevi can be detected at the molecular level, there are currently no established markers to predict biologic behavior. In part II of this continuing medical education article, we will review the molecular aspects of dysplastic nevi and their therapeutic implications. Our goal is to provide the clinician with an up-to-date understanding of this entity to facilitate clinical management of patients with nevi that have histologic dysplasia.
The "dysplastic" nevus
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Dysplastic nevi have become an increasing focus clinically, with evidence that they are associated with a higher risk of developing melanoma. However, there still is contention regarding the significance of dysplastic nevi. This contribution provides an overview of the history, epidemiology, genetics, clinical and histologic features, and procedures for clinical management of dysplastic nevi. Since dysplastic nevi were described originally in 1978, a great deal of research has examined the epidemiology of these lesions and the genetic factors related to the development of dysplastic nevi. However, there is disagreement regarding the clinical management of dysplastic nevi and the histologic definition of dysplastic nevi. Current recommendations include preventative measures, such as sun protection and careful surveillance and biopsies of suspicious lesions as needed. The advent of new technologies, such as computer-vision systems, have the potential to significantly change treatment of dysplastic nevi in the future.

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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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Regular ArticleGenetic Alterations ofp16INK4aandp53Genes in Sporadic Dysplastic Nevus☆,☆☆,★

Abstract

Genomics

Hum. Pathol.

J. Invest. Dermatol.

Biochem. Biophys. Res. Commun.

Cancer

Cancer

Arch. Derm.

Am. J. Dermatopath.

J. Med. Genet.

Science

Proc. Natl. Acad. Sci.

Nat. Genet.

Oncogene

Science

Am. J. Dermatopathol.

J. Epidermiol. Community Health

Regular Article
Genetic Alterations ofp16^INK4aandp53Genes in Sporadic Dysplastic Nevus☆,☆☆,★