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Unlocking the Secrets of Melanoma

Melanoma is a form of skin cancer that develops from melanocytes, which produce the pigment melanin. It is often characterized by the appearance of a dark, irregularly shaped mole on the skin. It is dangerous because it carries a greater risk of spreading to other parts of the body than other skin cancers. Melanoma can be fatal if not detected and treated early, but it is also one of the most preventable cancers. The best way to prevent melanoma is to protect the skin from UV radiation. You can either avoid prolonged exposure to the sun or use sunscreen to protect your skin.

Technologies for the diagnosis, prognosis and treatment of melanoma

However, melanoma is not caused solely by UV exposure. Rather, it arises by a combination of genetic and environmental factors, with genetic predisposition playing an important role. The American Joint Committee on Cancer (AJCC) proposed scoring parameters for clinical classification of melanoma. These parameters takes into consideration:

  • the thickness of the primary tumor (T) and its subcategory,

  • the presence of ulceration (erosion of the surface of a melanoma tumor, which can indicate a more advanced stage of disease),

  • the regional lymph node involvement (N),

  • and the presence of distant metastases (M).

The degree of vascular invasion (the process by which cancer cells enter and spread through the blood vessels in the body) is also important for determining the prognosis of a patient. The number of metastatic nodes and the presence of musculoskeletal injuries also play a role. Nowadays, the use of high-throughput technologies has allowed the discovery of new biomarkers and the characterization of the molecular landscape of melanoma. They may be useful for the diagnosis, prognosis and treatment of the disease.

In short, there are many biomarkers and significant genetic mutations associated with the development of melanoma. The epigenetic changes are complex, and there are a wide variety of technologies and many studies. It’s easy to get lost in the shuffle. Fortunately, a recently published study summarizes what we know about genomic and epigenomic alterations in melanoma. Furthermore, the authors discuss the latest scientific information.

Genetic mutations associated with melanoma

The review discusses various genetic mutations that are associated with the development of melanoma, a type of skin cancer. The first mutation discussed is the BRAF mutation, which is a common event in oncogenesis, particularly in melanoma. Studies have found that the presence of a BRAF mutation is associated with poor clinical outcome in melanoma. However, this remains controversial. The review also looks at the NRAS mutation, which is found in about 20% of melanomas. It is thought to contribute to the development of the cancer. Additionally, the authors talk about the NF1 mutation, which is a tumor suppressor gene that is often inactivated in melanomas. Studies have found that NF1 mutations are more common in acral and mucosal melanomas. Thus, they may be associated with resistance to treatment with BRAF inhibitors.

A recent meta-analysis genome-wide association study identified 54 significant locations (loci) and 68 independent SNPs (Single nucleotide polymorphisms) for melanoma. A brief explanation: SNPs are genetic variations that occur when a single nucleotide in a DNA sequence is different. These variants are associated with genes or loci located in the vicinity of genes involved in pathogenic pathways of melanoma such as DNA repair and telomere length (telomeres are the ends of linear chromosomes composed of repetitive DNA and associated proteins). They also play a role in melanocyte differentiation and cell adhesion, and in immunity.

Variants, loci and SNPs associated with telomere maintenance

The most common variants associated with melanoma that present a DNA repair pathway modification are rs78378222 and rs161548 at the TP53 locus. The loci and the SNPs associated with telomere maintenance correspond to the following genes: POT1, TERC, RTEL1, MPHOSPH6, STN1, CCND1, ATM, and PARP1. SNPs identified in following genes are implied in melanocyte development and differentiation pathway: FOXD3, NOTCH2, MITF, NOTCH1, and SOX10. E-cadherin encoded by the CDH1 gene plays a major role in the adhesion between melanocytes and keratinocytes. Common variants in immunity genes associated with melanoma susceptibility have been identified, for example, rs28986343 at the HLA locus and association between rs408825 and MX2 gene.

RNA molescules interfering with pathological processes

Circular RNAs (circRNAs) are endogenous RNA molecules with covalent loop structures that interfere with both normal physiological and pathological processes. They modulate transcription, splicing, microRNA sponging, protein-protein interaction modulation, and protein sponging. Some circRNA have oncogenic function and activate several physiological processes in melanoma, such as circ0084043 and circ-FOXM1, while others have suppressive function, such as circ0023988 and circ_0030388.

DNA methylation is a biochemical process in which a methyl group is added to a cytosine or adenine at the 5-position of the carbon, thereby suppressing gene expression. A study published in summarized genes hypermethylated in melanoma: LINE-1, CLDN11, TERT, MGMT, KIT, TNF, MITF, RASSF6, RASSF10, GPX3, MMP-9, SYNPO2, CDKN1C, LXN, ASC/PYCARDC/PYCARD, Col11A1, SOCS1, caspase 8, CDH1, MGMT, RAR-b2, CIITA-PIV, SOCS2, TNFRSF10C (DcR1/2), TPM1, TIMP3, CDKN2A, DPPIV, FRZB, SOCS3, THBS1, and TM. Last but not least, DNA methylation is also a significant predictor of longer overall survival in melanoma, as studies have shown.