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ウメガキ ノリコ
梅垣 知子 所属 医学部 医学科（附属足立医療センター） 職種 准教授 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Clonal Expansion of Second-Hit Cells with Somatic Recombinations or C>T Transitions Form Porokeratosis in MVD or MVK Mutant Heterozygotes. |
| 掲載誌名 | 正式名：The Journal of investigative dermatology 略 称：J Invest Dermatol ISSNコード：15231747/0022202X |
| 掲載区分 | 国外 |
| 巻・号・頁 | 139(12),pp.2458-2466.e9 |
| 著者・共著者 | Kubo Akiharu, Sasaki Takashi, Suzuki Hisato, Shiohama Aiko, Aoki Satomi, Sato Showbu, Fujita Harumi, Ono Noriko, Umegaki-Arao Noriko, Kawai Tomoko, Nakabayashi Kazuhiko, Hata Kenichiro, Yamada Daisuke, Matsubara Yoichi, Kosaki Kenjiro, Amagai Masayuki |
| 発行年月 | 2019/12 |
| 概要 | Patients with disseminated superficial actinic porokeratosis (DSAP) and linear porokeratosis (LP) exhibit monoallelic germline mutations in genes encoding mevalonate pathway enzymes, such as MVD or MVK. Here, we showed that each skin lesion of DSAP exhibited an individual second hit genetic change in the wild-type allele of the corresponding gene specifically in the epidermis, indicating that a postnatal second hit triggering biallelic deficiency of the gene is required for porokeratosis to develop. Most skin lesions exhibited one of two principal second hits, either somatic homologous recombinations rendering the monoallelic mutation biallelic or C>T transition mutations in the wild-type allele. The second hits differed among DSAP lesions but were identical in those of congenital LP, suggesting that DSAP is attributable to sporadic postnatal second hits and congenital LP to a single second hit in the embryonic period. In the characteristic annular skin lesions of DSAP, the central epidermis featured mostly second hit keratinocytes, and that of the annular ring featured a mixture of such cells and naïve keratinocytes, implying that each lesion reflects the clonal expansion of single second hit keratinocytes. DSAP is therefore a benign intraepidermal neoplasia, which can be included in the genetic tumor disorders explicable by Knudson's two-hit hypothesis. |
| DOI | 10.1016/j.jid.2019.05.020 |
| PMID | 31207227 |