Format

Send to

Choose Destination
See comment in PubMed Commons below
Mod Pathol. 2017 May;30(5):640-649. doi: 10.1038/modpathol.2016.237. Epub 2017 Feb 10.

Spitz nevi and Spitzoid melanomas: exome sequencing and comparison with conventional melanocytic nevi and melanomas.

Author information

1
Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA.
2
Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
3
School of Public Health, Yale University School of Medicine, New Haven, CT, USA.
4
Program in Computational Biology and Bioinformatics, Yale University School of Medicine, New Haven, CT, USA.

Abstract

We performed exome sequencing of 77 melanocytic specimens composed of Spitz nevi (n=29), Spitzoid melanomas (n=27), and benign melanocytic nevi (n=21), and compared the results with published melanoma sequencing data. Our study highlights the prominent similarity between Spitzoid and conventional melanomas with similar copy number changes and high and equal numbers of ultraviolet-induced coding mutations affecting similar driver genes. Mutations in MEN1, PRKAR1A, and DNMT3A in Spitzoid melanomas may indicate involvement of the protein kinase A pathway, or a role of DNA methylation in the disease. Other than activating HRAS variants, there were few additional mutations in Spitz nevi, and few copy number changes other than 11p amplification and chromosome 9 deletions. Similarly, there were no large-scale copy number alterations and few somatic alterations other than activating BRAF or NRAS mutations in conventional nevi. A presumed melanoma driver mutation (IDH1Arg132Cys) was revealed in one of the benign nevi. In conclusion, our exome data show significantly lower somatic mutation burden in both Spitz and conventional nevi compared with their malignant counterparts, and high genetic similarity between Spitzoid and conventional melanoma.

PMID:
28186096
PMCID:
PMC5413430
[Available on 2017-08-10]
DOI:
10.1038/modpathol.2016.237
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center