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.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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
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 Adoi
10.1038/s41467-017-00758-3subject
Has Abstractpub_date
2017-09-21 00:00:00pages
644issue
1issn
2041-1723pii
10.1038/s41467-017-00758-3journal_volume
8pub_type
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