Combined activation of MAP kinase pathway and β-catenin signaling cause deep penetrating nevi

Iwei Yeh (), Ursula E. Lang, Emeline Durieux, Meng Kian Tee, Aparna Jorapur, A. Hunter Shain, Veronique Haddad, Daniel Pissaloux, Xu Chen, Lorenzo Cerroni, Robert L. Judson, Philip E. LeBoit, Timothy H. McCalmont, Boris C. Bastian and Arnaud de la Fouchardière
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Iwei Yeh: University of California
Ursula E. Lang: University of California
Emeline Durieux: Centre Hospitalier Lyon-Sud
Meng Kian Tee: University of California
Aparna Jorapur: University of California
A. Hunter Shain: University of California
Veronique Haddad: Centre Léon Bérard
Daniel Pissaloux: Centre Léon Bérard
Xu Chen: University of California
Lorenzo Cerroni: Medical University of Graz
Robert L. Judson: University of California
Philip E. LeBoit: University of California
Timothy H. McCalmont: University of California
Boris C. Bastian: University of California
Arnaud de la Fouchardière: Centre Léon Bérard

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00758-3

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