title: Spitz nevi and Spitzoid melanomas: exome sequencing and comparison with conventional melanocytic nevi and melanomas.
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.
authors.affiliation: Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA.|Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Rossitza
authors.initials: R
authors.lastname: Lazova
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Natapol
authors.initials: N
authors.lastname: Pornputtapong
authors.affiliation: Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Halaban
authors.affiliation: Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA.|Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bosenberg
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Yalai
authors.initials: Y
authors.lastname: Bai
authors.affiliation: School of Public Health, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Chai
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.|Program in Computational Biology and Bioinformatics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Krauthammer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D018332:Nevus, Epithelioid and Spindle Cell / Q000235:genetics*; D009508:Nevus, Pigmented / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor