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Brief Report
January 2, 2019

Use of Targeted Next-Generation Sequencing to Identify Activating Hot Spot Mutations in Cherry Angiomas

Author Affiliations
  • 1Medical student, Wellman Center for Photomedicine at Massachusetts General Hospital, Harvard Medical School, Boston
  • 2Department of Dermatology, Massachusetts General Hospital, Boston
  • 3Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston
  • 4Wellman Center for Photomedicine at Massachusetts General Hospital, Harvard Medical School, Boston
  • 5Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston
  • 6Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston
JAMA Dermatol. Published online January 2, 2019. doi:10.1001/jamadermatol.2018.4231
Key Points

Question  Which somatic mutations are found in benign cherry angiomas?

Findings  In a case series of 10 cherry angioma tissue samples, 5 samples were found to have activating hot spot mutations in GNAQ (Q209H, Q209R, and R183G) and GNA11 (Q209H) genes.

Meaning  Cherry angiomas frequently carry specific genetic variants, which are known to be involved in pathways underlying vascular conditions, such as congenital hemangiomas, hepatic small-vessel neoplasms, port-wine stains, and Sturge-Weber syndrome, as well as melanocytic proliferations, such as blue nevi, melanoma associated with blue nevus, and uveal melanoma.

Abstract

Importance  Shared gene variants in benign-malignant process pairs, such as BRAF mutations common to benign nevi and melanoma, are associated with differing phenotypic manifestations. Study of gene mechanisms underlying cherry angioma may uncover previously unknown disease relationships.

Objective  To identify somatic mutations present in cherry angioma specimens by using targeted next-generation sequencing.

Design, Setting, and Participants  In a single-center case series, 10 formalin-fixed, paraffin-embedded cherry angioma specimens from biopsies performed at Massachusetts General Hospital in Boston from July 10, 2016, to January 23, 2018, were obtained and underwent sequencing across a panel of 323 genes most relevant to cancer. Somatic mutations were curated by excluding variants that were presumed to be germline or of low mapping quality.

Main Outcomes and Measures  Identification of somatic mutations associated with cherry angiomas.

Results  In 10 cherry angioma tissue samples originating from 6 female and 4 male patients with a median (range) age of 54 (26-79) years, 5 samples (50%) revealed somatic missense mutations in GNAQ (Q209H, Q209R, and R183G) and GNA11 (Q209H). Individually, these mutational hot spots are known to be involved in entities that include congenital and anastomosing hemangiomas, hepatic small-vessel neoplasms (Q209), port-wine stains, and Sturge-Weber syndrome (R183). Both hot spots are associated with blue nevi, melanoma associated with blue nevus, and uveal melanoma.

Conclusions and Relevance  In this case series study, the high prevalence of 5 known genetic drivers within the benign cherry angioma entity appears to support the context-dependent role of gene alterations in both benign and malignant proliferations from various cellular origins.

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