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. 2021 Jul 1;157(7):831-835.
doi: 10.1001/jamadermatol.2021.0793.

A Mutational Survey of Acral Nevi

Keiran S M Smalley  1   2 , Jamie K Teer  3 , Y Ann Chen  3 , Jheng-Yu Wu  1 , Jiqiang Yao  4 , John M Koomen  5 , Wei-Shen Chen  6 , Paul Rodriguez-Waitkus  6 , Florian A Karreth  5 , Jane L Messina  2
Affiliations

A Mutational Survey of Acral Nevi

Keiran S M Smalley et al. JAMA Dermatol. .

Abstract

Importance: Acral skin may develop nevi, but their mutational status and association with acral melanoma is unclear.

Objective: To perform targeted next-generation sequencing on a cohort of acral nevi to determine their mutational spectrum.

Design, setting, and participants: Acral nevi specimens (n = 50) that had been obtained for diagnostic purposes were identified from the pathology archives of a tertiary care academic cancer center and a university dermatology clinic. Next-generation sequencing was performed on DNA extracted from the specimens, and mutations called. A subset of samples was stained immunohistochemically for the BRAF V600E mutation.

Results: A total of 50 nevi from 49 patients (19 males and 30 females; median [range] age, 48 [13-85] years) were examined. Analysis of the sequencing data revealed a high prevalence of BRAF mutations (n = 43), with a lower frequency of NRAS mutations (n = 5). Mutations in BRAF and NRAS were mutually exclusive.

Conclusions and relevance: In this cohort study, nevi arising on mostly sun-protected acral skin showed a rate of BRAF mutation similar to that of acquired nevi on sun-exposed skin but far higher than that of acral melanoma. These findings are in contrast to the well-characterized mutational landscape of acral melanoma.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Smalley reported receiving grants from the Melanoma Research Alliance and the National Institutes of Health during the conduct of the study and personal fees (honoraria for serving as an editor) from Elsevier outside the submitted work. Dr Teer reported receiving grants from the Melanoma Research Foundation and the National Cancer Institute (P30-CA76292) during the conduct of the study; in addition, Dr Teer had a patent pending for Negative Storage Model for genomic information. Dr Koomen reported receiving grants from the National Cancer Institute (CCSG P30-CA076292) during the conduct of the study. Drs Karreth and Messina reported receiving grants from the Melanoma Research Alliance during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. Oncogenic Driver Mutations in Acral Nevi
A, Oncoprint of mutations in common acral and cutaneous melanoma genes found in the cohort of acral nevi (n = 50). Data show the identified mutations in each nevus by sequencing. Red boxes indicate protein-altering mutations. Gray boxes indicate lesions from the dorsal foot. Each column represents a different sample. B, Representative immunohistochemical analysis of mutant BRAF V600E staining in acral nevi with a confirmed BRAF V600E mutation by next-generation sequencing. C, BRAF V600E staining.
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References

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