Cutaneous melanoma (CM) is known as an aggressive malignant cancer; some of which are directly derived from melanocytic nevi, which have been attracting growing attention from the last decades.,This study focused on comprehensive identification, validation, and functional annotations of prognostic differentially expressed genes (DEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles.,DEGs were obtained using three chip datasets from GEO database to identify after standardization annotation.,A total of 73 DEGs were identified as possible candidate prognostic biomarkers between melanocytic nevus and malignant melanoma.,In addition, survival curves indicated that six hub genes, including FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2, were significant prognostic signatures for CM and of significant value to predict transformation from nevi to melanoma.,Furthermore, immunohistochemistry staining was performed to validate differential expression levels and prognostic implications of six hub genes between CM tissue and nevus tissues from the First Affiliated Hospital of Soochow University cohort.,It suggested that significantly elevated FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2 proteins expressed in the CM than in the nevus tissues.,Functional enrichment and significant pathways of the six significant hub genes indicated that the mostly involved hallmarks include the P53 pathway, K-ras signaling, estrogen response late, and estrogen response early.,In summary, this study identified significant DEGs participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles.,Transcription profiles of FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2 provided clues of prognostic implications, which might help us evaluate malignant potential of nevus and underlying carcinogenesis progress from melanocytic nevus to melanoma.
Analysis of melanomas for actionable mutations has become the standard of care.,Recently, a classification scheme has been proposed that categorizes BRAF mutations based on their mechanisms for activation of the MAPK pathway.,In this analysis BRAF, KIT, NRAS, and PIK3CA mutations were examined by next generation sequencing (NGS) in 446 melanomas in a clinical diagnostic setting.,KRAS and HRAS were also analyzed to elucidate coexisting BRAF and RAS mutations.,BRAF mutations were categorized into class-1 (kinase-activated, codon 600), class-2 (kinase-activated, non-codon 600) and class-3 (kinase-impaired), based on the newly proposed classification scheme.,NGS demonstrated high analytic sensitivity.,Among 355 mutations detected, variant allele frequencies were 2-5% in 21 (5.9%) mutations and 2-10% in 47 (13%) mutations.,Mutations were detected in BRAF (42%), NRAS (25%), KIT (4.9%) and PIK3CA (2.7%).,The incidence of class-1, class-2 and class-3 mutations were 33% (26% p.V600E and 6.1% p.V600K), 3.1 and 4.9% respectively.,With a broader reportable range of NGS, class-1, class-2 and class-3 mutations accounted for 77, 7.4 and 12% of all BRAF mutations.,Class-3 mutations, commonly affecting codons 594, 466 and 467, showed a higher incidence of coexisting RAS mutations, consistent with their RAS-dependent signaling.,Significant association with old age and primary tumors of head/neck/upper back suggest chronic solar damage as a contributing factor for melanomas harboring BRAF p.V600K or class-3 mutations.,This study categorizes the range, frequency, coexisting driver mutations and clinical characteristics of the three classes of BRAF mutations in a large cohort of melanomas in a clinical diagnostic setting.,Further prospective studies are warranted to elucidate the clinical outcomes and benefits of newly developed targeted therapy in melanoma patients carrying each class of BRAF mutation.,The online version of this article (10.1186/s12885-019-5864-1) contains supplementary material, which is available to authorized users.