BRAF wild-type melanoma in situ arising in a BRAF V600E mutant dysplastic nevus

IMPORTANCE The BRAF V600E mutation accounts for the majority of BRAF mutations found in cutaneous melanoma and is also commonly found in nevi. We used dermoscopy-targeted sampling and a microbiopsy device coupled with DNA sequence analysis to highlight BRAF V600E heterogeneity within a multicomponent melanocytic proliferation. This sampling technique demonstrates the prospect of in vivo application in a clinical setting

Whole-exome sequencing of acquired nevi identifies mechanisms for development and maintenance of benign neoplasms

The melanoma transformation rate of each nevus is rare despite the detection of oncogenic BRAF or NRAS mutations in 100% of nevi. Acquired melanocytic nevi (AMN) do however mimic melanoma and ∼30% of all melanomas arise within pre-existing nevi. Using whole-exome sequencing of 30 matched nevi, adjacent normal skin, and saliva we sought to identify the underlying genetic mechanisms for nevus development. All nevi were clinically, dermoscopically, and histopathologically documented. In addition to identifying somatic mutations, we found mutational signatures relating to ultra-violet radiation (UVR) mirroring those found in cutaneous melanoma. In nevi we frequently observed the presence of the UVR mutation signature compared to adjacent normal skin (97% vs 10% respectively). In copy number aberration (CNA) analysis, in nevi with copy number loss of tumor suppressor genes (TSG), these were balanced by loss of potent oncogenes. Moreover, reticular and non-specific patterned nevi revealed an increased (

BRAFV600E Mutation Status of Involuting and Stable Nevi in Dabrafenib Therapy with or without Trametinib

IMPORTANCE Recent advances in targeting BRAF(V600E) mutations, which occur in roughly 50% of melanomas and 70% of benign nevi, have improved response rates and survival in patients with melanoma. With increased survival, the importance of other comorbidities increases and requires consideration in long-term management. This case report discusses dynamic dermoscopic nevus changes that occur during dabrafenib therapy and offers some conclusions regarding BRAF mutations and the changes

Acquired Melanocytic Nevi Images documented with dermoscopy, pigmentation characteristics and MC1R genotypes in a Han Chinese population

Aquired melanocytic neviMelanocortin-1 receptorPigmentationDermoscop

High incidence of primary melanomas in an MC1R RHC homozygote/CDKN2A mutant genotype patient

Melanoma incidence in Australia remains the highest in the world; hence understanding its causation is paramount for future therapeutic developments. Multiple primary melanomas are also common occurrences among the Australian population with identified risk factors such as personal and family history of melanoma, fair skin type, dysplastic naevus syndrome and history of significant ultraviolet exposure. The roles of both environmental and genetic factors have been elucidated in melanoma development, but the synergy of interactions between the two remains complex given the heterogeneous nature of the disease. We present a rare case of a 57-year-old female with 20 cutaneous melanomas and review the role of genetic and environmental factors in development of her multiple primary melanomas

Skin pigmentation genetics for the clinic

Human pigmentation characteristics play an important role in the effects of sun exposure, skin cancer induction and disease outcomes. Several of the genes most important for this diversity are involved in the regulation and distribution of melanin pigmentation or enzymes involved in melanogenesis itself within the melanocyte cell present in the skin, hair and eyes. The single nucleotide polymorphisms and extended haplotypes within or surrounding these genes have been identified as risk factors for skin cancer, in particular, melanoma. These same polymorphisms have been under selective pressure leading towards lighter pigmentation in Europeans in the last 5,000- 20,000 years that have driven the increase in frequency in modern populations. Although pigmentation is a polygenic trait, due to interactive and quantitative gene effects, strong phenotypic associations are readily apparent for these major genes. However, predictive value and utility are increased when considering gene polymorphism interactions. In melanoma, an increased penetrance is found in cases when pigmentation gene risk alleles such as MC1R variants are coincident with mutation of higher- risk melanoma genes including CDKN2A, CDK4 and MITF E318K, demonstrating an interface between the path-ways for pigmentation, naevogenesis and melanoma. The clinical phenotypes associated with germline changes in pigmentation and naevogenic genes must be understood by clinicians, and will be of increasing relevance to dermatologists, as genomics is incorporated into the delivery of personalised medicine. (C) 2017 S. Karger AG, Basel