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.

中文翻译：

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MAP激酶途径和β-catenin信号传导的联合激活会引起深度穿透痣。

深部穿透痣（DPN）的特征是黑色素细胞扩大，穿过真皮。DPN很难与黑色素瘤区分开，但很少表现出侵略性的生物学行为。在这里，我们确定了β-连环蛋白和丝裂原激活的蛋白激酶途径的突变组合作为DPN的特征。β-catenin途径的突变将具有BRAF突变的普通痣的表型改变为DPN的表型，从而增加了色素沉着，细胞体积和细胞周期蛋白D1水平。我们的研究结果表明，本构性β-catenin途径活化通过超越对普通痣增殖的微环境依赖性来促进肿瘤发生。在由DPN引起的黑色素瘤中，我们发现了其他致癌性改变。我们确定DPN是从痣到黑色素瘤逐步发展的中间阶段。总而言之，我们描述了特定的遗传改变及其顺序，这些信息可以帮助对这些独特的肿瘤进行诊断分类和分级。深穿透痣（DPN）是罕见的具有未知遗传驱动因素的黑素细胞性肿瘤。在这里，作者表明大多数DPN在β-catenin和MAP激酶途径中都具有激活突变。这种特征可以帮助对这些独特的肿瘤进行分类和分级。深穿透痣（DPN）是罕见的具有未知遗传驱动因素的黑素细胞性肿瘤。在这里，作者表明大多数DPN在β-catenin和MAP激酶途径中都具有激活突变。这种特征可以帮助对这些独特的肿瘤进行分类和分级。深穿透痣（DPN）是罕见的具有未知遗传驱动因素的黑素细胞性肿瘤。在这里，作者表明大多数DPN在β-catenin和MAP激酶途径中都具有激活突变。这种特征可以帮助对这些独特的肿瘤进行分类和分级。