Melanoma is one of the most common types of malignancy in the world, and one known to carry a very poor prognosis until recent years. This review aims to outline the events in the history of the disease and the impact made by the discoveries along the way, as well as the modern-day consensus by referencing the updated literature regarding the present approach and future directions. In the last two decades, several studies and research have brought significant improvement in the diagnosis and clinical management of melanomas. The development of sentinel lymph node biopsy has brought major changes to the surgical approach to the disease, and modern therapies based on recently developed knowledge changed the death sentence this diagnosis once meant to a manageable condition despite its aggressiveness, keeping in mind that early diagnosis and safe margin excision remain the best and most optimistic course of treatment.
Background: Head and neck cancers, and particularly, oral cancers have a complex pathogenesis that includes genetic mutations and epigenetic alterations which interfere with cellular signaling and can trigger tumor development. The purpose of this study was to reveal whether low-frequency hotspot mutations may be detected in a study lot with histopathological evidence of squamous cell carcinoma (SCC) of the oral mucosa and skin of the head and neck. Methods: Tumor biopsies from treatment- naïve patients were tested for BRAF V600, NRAS G12/G13, NRAS Q61, KRAS Q61 mutations, and EGFR exon 19 deletions (Ex19Del) using droplet digital PCR (ddPCR). The tumors were also analyzed for EGFR T790M mutations by RT-PCR, using a CE-IVD validated kit, with a limit of detection of 0.05%. Results: None of the examined cases exhibited NRAS G12/G13, NRAS Q61, KRAS Q61, BRAF V600, or EGFR T790M mutations, indicating that these alterations are rare events in SCC pathogenesis. Interestingly, among the 12 specimens tested by ddPCR for EGFR Ex19Del, an HPV-negative cSCC tumor occurring in the parotid region tested positive for this drug-sensitizing mutation, offering unexplored therapeutic perspectives to the patient from whom it was collected. Conclusions: Our study highlights the important clinical implications of detecting low-frequency hotspot mutations in tumor biopsies by ddPCR. We believe that the ddPCR-assisted analysis of these mutations in larger SCC cohorts may provide us with mechanistic insights regarding their role in SCC pathogenesis and guide the development of novel therapeutic strategies for this problematic disease.
