High frequency of PTEN mutations in nevi and melanomas from xeroderma pigmentosum patients. (21st February 2014)

• Record Type: Journal Article
• Authors: Masaki, Taro; Wang, Yun; DiGiovanna, John J.; Khan, Sikandar G.; Raffeld, Mark; Beltaifa, Senda; Hornyak, Thomas J.; Darling, Thomas N.; Lee, Chyi‐Chia R.; Kraemer, Kenneth H.
• Is Part Of: Pigment cell & melanoma research. Volume 27:Number 3(2014:May)
• Page Start: 454
• Page End: 464
• Publication Date: 2014-02-21
• Subjects: Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12226
• Languages: English
• ISSNs: 1755-1471

Abstract

<abstract abstract-type="main" id="pcmr12226-abs-0001"> <title>Summary</title> <p>We examined nevi and melanomas in 10 xeroderma pigmentosum (XP) patients with defective DNA repair. The lesions had a lentiginous appearance with markedly increased numbers of melanocytes. Using laser capture microdissection, we performed DNA sequencing of 18 benign and atypical nevi and 75 melanomas (melanoma in situ and invasive melanomas). The nevi had a similar high frequency of <italic>PTEN</italic> mutations as melanomas [61% (11/18) versus 53% (39/73)]. Both had a very high proportion of UV‐type mutations (occurring at adjacent pyrimidines) [91% (10/11) versus 92% (36/39)]. In contrast to melanomas in the general population, the frequency of <italic>BRAF</italic> mutations (11%, 7/61), <italic>NRAS</italic> mutations (21%, 13/62), and <italic>KIT</italic> mutations (21%, 6/28) in XP melanomas was lower than for <italic>PTEN</italic>. Phospho‐S6 immunostaining indicated activation of the mTOR pathway in the atypical nevi and melanomas. Thus, the clinical and histological appearances and the molecular pathology of these UV‐related XP nevi and melanomas were different from nevi and melanomas in the general population.</p> </abstract>