Melanoma Diagnosis and Patient Management

Melanoma arises from malignant transformation of melanocytes and is notable for its rapid progression and high metastatic potential. Early detection through clinical examination and dermoscopic evaluation remains the cornerstone of diagnosis, supplemented by histopathological assessment of excised lesions. Staging relies on tumour thickness, ulceration status and nodal involvement, guiding decisions on sentinel lymph node biopsy and imaging. Molecular profiling, particularly for BRAF, NRAS and KIT mutations, informs targeted therapy selection, while immunohistochemical markers aid prognostic stratification. Patient management has evolved to integrate surgical excision, systemic targeted agents, immune checkpoint inhibitors and adjuvant therapies, tailored to disease stage and mutational status. Multidisciplinary care teams coordinate surveillance schedules and address long-term follow-up, psychosocial support and preventive counselling. Advances in liquid biopsy and artificial intelligence are poised to augment real-time monitoring and refine personalised treatment pathways, underscoring the global imperative to translate molecular insights into improved outcomes for diverse patient populations.

Research from Nature Portfolio

Comprehensive exome sequencing of acral melanoma has revealed that the majority of tumours display punctuated copy number transitions with focal amplifications on chromosomes 5, 11, 12 and 22. Early activation of the telomerase reverse transcriptase gene precedes later mutations in the MAPK signalling cascade, indicating an inverted evolutionary sequence that may underpin therapeutic resistance. Intratumoral heterogeneity in MAPK pathway alterations offers an explanation for the variable response to kinase inhibitors in this subtype. Separately, whole-genome analysis of mucosal melanoma has uncovered a low burden of point mutations but a high frequency of structural variants, including recurrent rearrangements targeting TERT, CDK4 and MDM2. Mutations in NRAS, BRAF, NF1, KIT and SF3B1 define potential molecular subgroups, and the prevalence of WNT pathway defects implicates novel therapeutic avenues. Together, these studies highlight the central role of genomic architecture in guiding precision treatment strategies for rare melanoma subtypes.

Melanoma Diagnosis and Patient Management publication trend

The graph below shows the total number of articles in melanoma diagnosis and patient management across all publications each year (not limited to Nature Index journals).

Technical terms

Acral melanoma: A melanoma subtype arising on palms, soles or under nails, often genetically distinct from cutaneous forms.

Copy number transition: A genomic alteration involving gains or losses of large DNA segments that can amplify oncogenes or delete tumour suppressors.

TERT: Telomerase reverse transcriptase, an enzyme component that maintains telomere length and is frequently upregulated in cancer.

MAPK pathway: Mitogen-activated protein kinase signalling cascade that regulates cell proliferation and is commonly mutated in melanoma.

Structural variant: A large-scale genomic rearrangement such as translocation, inversion or large insertion/deletion.

BRAF mutation: A genetic alteration, often V600E, activating the BRAF kinase and driving uncontrolled cell growth.

Immune checkpoint inhibitor: A class of immunotherapy that blocks inhibitory pathways (e.g. PD-1, CTLA-4) to enhance T-cell–mediated tumour eradication.

Phenotype switching: The reversible transition of melanoma cells between proliferative and invasive states, contributing to metastasis and drug resistance.

References

1. The genetic evolution of acral melanoma. Nature Communications (2024).
2. Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets. Nature Communications (2019).
3. Reduced Melanoma After Regular Sunscreen Use: Randomized Trial Follow-Up. Journal of Clinical Oncology (2010).
4. The global burden of melanoma: results from the Global Burden of Disease Study 2015. British Journal of Dermatology (2017).
5. Comparison of high resolution melting analysis, pyrosequencing, next generation sequencing and immunohistochemistry to conventional Sanger sequencing for the detection of p.V600E and non-p.V600E BRAFmutations. BMC Cancer (2014).
6. Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Modern Pathology (2017).
7. Phenotype Switching in Melanoma: Implications for Progression and Therapy. Frontiers in Oncology (2015).