Combined activation of MAP kinase pathway and β-catenin signaling cause deep penetrating nevi.
Combined activation of MAP kinase pathway and β-catenin signaling cause deep penetrating nevi.
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DOI：
10.1038/s41467-017-00758-3
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发表时间：
2017-09-21
影响因子：
16.6
通讯作者：
de la Fouchardière A
中科院分区：
文献类型：
--
作者：
Yeh I;Lang UE;Durieux E;Tee MK;Jorapur A;Shain AH;Haddad V;Pissaloux D;Chen X;Cerroni L;Judson RL;LeBoit PE;McCalmont TH;Bastian BC;de la Fouchardière A
深穿透痣（DPN）的特点是扩大，色素黑素细胞延伸通过真皮。DPN可能难以与黑色素瘤区分，但很少显示侵袭性生物学行为。在这里，我们确定了β-连环蛋白和丝裂原活化蛋白激酶途径的突变组合作为DPN的特征。β-catenin通路的突变将BRAF突变的常见痣表型改变为DPN，色素沉着、细胞体积和核细胞周期蛋白D1水平增加。我们的研究结果表明，组成性β-连环蛋白通路激活促进肿瘤的发生，压倒依赖于微环境，限制增殖的共同痣。在DPN引起的黑色素瘤中，我们发现了额外的致癌改变。我们将DPN确定为从痣到黑色素瘤逐步进展的中间阶段。总之，我们描述了特定的遗传改变及其顺序，这些信息可以帮助这些独特的肿瘤的诊断分类和分级。深穿透痣（DPN）是一种罕见的黑素细胞肿瘤，其遗传驱动因素未知。在这里，作者表明大多数DPN在β-连环蛋白和MAP激酶通路中具有激活突变;这一特征有助于这些独特肿瘤的分类和分级。
Deep penetrating nevus (DPN) is characterized by enlarged, pigmented melanocytes that extend through the dermis. DPN can be difficult to distinguish from melanoma but rarely displays aggressive biological behavior. Here, we identify a combination of mutations of the β-catenin and mitogen-activated protein kinase pathways as characteristic of DPN. Mutations of the β-catenin pathway change the phenotype of a common nevus with BRAF mutation into that of DPN, with increased pigmentation, cell volume and nuclear cyclin D1 levels. Our results suggest that constitutive β-catenin pathway activation promotes tumorigenesis by overriding dependencies on the microenvironment that constrain proliferation of common nevi. In melanoma that arose from DPN we find additional oncogenic alterations. We identify DPN as an intermediate stage in the step-wise progression from nevus to melanoma. In summary, we delineate specific genetic alterations and their sequential order, information that can assist in the diagnostic classification and grading of these distinctive neoplasms. Deep penetrating nevi (DPN) are unusual melanocytic neoplasms with unknown genetic drivers. Here the authors show that majority of DPN harbor activating mutations in the β-catenin and the MAP-kinase pathways; this characteristic can help in the classification and grading of these distinctive neoplasms.
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DOI：
10.1016/s0190-9622(08)81502-2
发表时间：
1994-05-01
影响因子：
13.8
作者：
BALL, NJ;GOLITZ, LE
通讯作者：
GOLITZ, LE
影响因子：
2.9
作者：
Fischmann, Thierry O.;Smith, Catherine K.;Madison, Vincent S.
通讯作者：
Madison, Vincent S.
影响因子：
30.8
作者：
Nikolaev, Sergey I.;Rimoldi, Donata;Antonarakis, Stylianos E.
通讯作者：
Antonarakis, Stylianos E.
影响因子：
10.5
作者：
Delmas, Veronique;Beermann, Friedrich;Larue, Lionel
通讯作者：
Larue, Lionel
影响因子：
20.3
作者：
Chakraborty, Rikhia;Hampton, Oliver A.;Parsons, D. Williams
通讯作者：
Parsons, D. Williams