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Melanoma represents just 1% of skin cancer but is responsible for the vast majority of skin cancer deaths. Given its implications for therapeutic advancement, the field of melanoma genomics has dramatically expanded in recent years. At one time classified mainly by anatomical location-non-acral cutaneous melanoma (NACM), acral cutaneous melanoma (ACM), mucosal melanoma (MuM), or uveal melanoma (UM) are now further sub-classified based on the mutated genes that drive their initiation, progression, and survival. BRAF gene mutations in NACM are the most frequently occurring and the best-studied, giving rise to the successful use of BRAF inhibitors in clinical practice for the last decade. This development has opened the door for many promising clinical trials and countless investigations into melanoma's genetic underpinnings. In this review, we offer an overview of melanoma genomics and discuss the most relevant somatic mutations such as BRAF, NRAS, and NF1 in NACM, KIT in ACM and MuM, and GNAQ, GNA11, and BAP1 in UM. Particular emphasis is placed on the biochemical pathways driven by each mutation, their associated clinical manifestations, and their role as current and future therapeutic targets.

Although TERT promoter mutations have been associated with a worsened prognosis in melanoma, the relationship between mutation status and downstream telomerase activity and telomere length remains convoluted. Using Sanger sequencing and techniques based on quantitative reverse transcriptase in real time, we evaluated 60 melanoma cell lines for TERT promoter mutational status, copy number, gene expression, and telomere length to provide a comprehensive analysis of the TERT/telomere pathway and establish a classification system whereby the associations between TERT mutations and their downstream molecular manifestations can more easily be ascertained. Mutations at positions -124/125 and -146 were associated with the highest levels of TERT gene expression but had no appreciable impact on absolute telomere length. In contrast, the common variant rs2853669 (at position -245) was significantly associated with longer telomere length via a recessive model in our cohort (P ¼ 0.003). Our results, which are from assays performed on purified melanoma cell lines, suggest that the TERT promoter harbors a more complex mutational landscape than previously thought. Furthermore, the failure of TERT promoter mutations to consistently correlate with TERT expression and telomere length suggests an alternative method whereby tumor cells escape the critical shortening of telomeres.

This article addresses reflections of one University instructor’s teaching and her pre-teacher education students’ innovative digital learning practices during the Covid-19 pandemic in Spring 2020. The question of How has one instructor embedded digital practices in her virtual teaching to engage and purposefully introduce and connect pre-teacher education students with diverse technologies and multimodalities of learning during a mandatory virtual instruction time? will be addressed and discussed. Student-centered practices such as group work, pair work, the use of Zoom breakout rooms, and multimodal literary responses through technology applications such as Flipgrid and Google Docs will be described and reflected upon. The instructor’s own teaching practices that have included weekly mentoring meetings with her education students and continuing individual coffee meetings in diverse settings will be highlighted as ways of demonstrating care and encouragement toward face-to-face students who have been transitioned as online students. The reflections outlined in this abstract draw upon the notion of technologies as providers of active interactions and will include snapshots of an instructors’ students’ digital artifacts such as Flipgrid, video-recorded monologues, and Google Doc news stories with students reflecting on the uses of multimodal technologies in their own future teaching practices. This manuscript will also include student reflections and a sidebar of suggestions for using Zoom with virtual teaching.

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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 PARTICIPANTSIn 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. RESULTSIn 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 RELEVANCEIn 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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