# Molecular Profile of Skin Cancer
## 3 Gene Mutations in Melanoma
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Author, Year** & **BRAF Detection Method** & & **Results and Conclusion** \\ \hline \multirow{8}{*}{[PERSON] et al., 2021} & & \(\bullet\) & CTCs are present even in the early stage of melanoma, and the number of CTCs seems to reflect patients’ responses to BRAF/MEK inhibitor treatment. \\  & \(\bullet\) & Circulating tumor cells (CTCs) were isolated from peripheral blood using a high-density dielectrophoretic & \(\bullet\) & Genetic heterogeneity of BRAF may contribute to resistance to BRAF/MEK inhibitors. \\  & \(\bullet\) & Microbial tumor DNA (ctDNA) Droplet digital polymerase chain reaction assays were designed for ctDNA detection. & \(\bullet\) & The usefulness of CTC analysis for monitoring responses to targeted therapies in melanoma patients, and for understanding the mechanism of drug resistance. \\  & \(\bullet\) & Whole exome sequencing of ctDNA was also conducted in 9 patients & \(\bullet\) & Trend of high TMB and neoepitope load in responders compared to non-responders. \\  & \(\bullet\) & Promoting tumor mutations (TMB) and neoepitope load measurements. & \(\bullet\) & Changes in ctDNA can serve as an early indicator of outcomes in metastatic melanoma patients treated with systemic therapies and, therefore, may serve as a tool to guide treatment decisions. \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Modern methods for BRAF detection. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Author, Year** & **BRAF Detection Method** & & **Results and Conclusion** \\ \hline [PERSON] et al., 2020 & \(\bullet\) & To standardize a liquid biopsy platform to identify hotspot mutations in BRAF, NRAS and TERT in plasma samples from advanced melanoma patients and investigate whether it was associated to clinical outcome. & We established a specific and sensitive methodology with a LOD ranging from 0.13 to 0.37\%, and LOB ranging from of 0 to 5.201 copies/reaction. & Somatic mutations occurred in 17/19 (89\%) patients, of whom seven (41\%) had ctDNA detectable their paired plasma. ctDNA detection was associated with shorter progression free survival (\(p=0.01\)). & The protocol improves the detection of BRAFV600E gene copies in comparison to the reference protocol for ctDNA isolation. \\ [PERSON] et al., 2020 & \(\bullet\) & Clinical practice-compatible protocol for the isolation of EV-DNA and assessed BRAF gene status on plasma samples from metastatic melanoma patients at the beginning and during BRAFi therapy. & \(\bullet\) \\ \hline \hline \end{tabular}
\end{table} 
Table 2: _Cont._Another limitation of this screening method is the existence of melanomas that do not contain canonical BRAF-mutations. One good example could be the study conducted by [PERSON] et al. regarding a patient with two metastases that were the hallmark of sample-specific mutations was absent. Mutations in MAP2K1 and MAP2K2 genes (MEK1 and MEK2, respectively) were found, resulting in higher resistance to MEK inhibitors because of the constitutive ERK phosphorylation [29]. Because these mutations can occur in 8% of melanomas, with negative consequences on the therapy (resistance to conventional chemotherapy), they must be taken into account. Given the cancer-related dysregulation of different signaling pathways, for satisfactory clinical outcomes, the ideal therapy should be a combination therapy targeting different sites of several signaling pathways. This is supported by the fact that dacarbazine is effective only in 15-20% of patients with melanoma [30]. Besides the extensive studies regarding the BRAF mutations, researchers recently found other gene mutations that might be involved in the pathophysiology of melanoma and NMSC. An example could be the ER (estrogen related receptor) gene, studies of which have just begun, following the results of studies that showed a lower incidence of MM in women than in men. However, only few articles are available on this topic, the effects of ER gene in the modulation of metabolism and cancer being still intensively studied [31].