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High frequency of PTEN mutations in nevi and melanomas from xeroderma pigmentosum patients
Author(s) -
Masaki Taro,
Wang Yun,
DiGiovanna John J.,
Khan Sikandar G.,
Raffeld Mark,
Beltaifa Senda,
Hornyak Thomas J.,
Darling Thomas N.,
Lee ChyiChia R.,
Kraemer Kenneth H.
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12226
Subject(s) - xeroderma pigmentosum , neuroblastoma ras viral oncogene homolog , pten , melanoma , nevus , pathology , population , medicine , mutation , dermatology , cancer research , biology , genetics , dna repair , dna , gene , apoptosis , environmental health , pi3k/akt/mtor pathway , kras
Summary 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 PTEN 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 BRAF mutations (11%, 7/61), NRAS mutations (21%, 13/62), and KIT mutations (21%, 6/28) in XP melanomas was lower than for PTEN . Phospho‐S6 immunostaining indicated activation of the m TOR 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.