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Review
. 2021 Dec 28;14(1):123.
doi: 10.3390/cancers14010123.

Genomic and Transcriptomic Underpinnings of Melanoma Genesis, Progression, and Metastasis

Olga S Cherepakhin  1 , Zsolt B Argenyi  2 , Ata S Moshiri  2   3
Affiliations
Review

Genomic and Transcriptomic Underpinnings of Melanoma Genesis, Progression, and Metastasis

Olga S Cherepakhin et al. Cancers (Basel). .

Abstract

Melanoma is a deadly skin cancer with rapidly increasing incidence worldwide. The discovery of the genetic drivers of melanomagenesis in the last decade has led the World Health Organization to reclassify melanoma subtypes by their molecular pathways rather than traditional clinical and histopathologic features. Despite this significant advance, the genomic and transcriptomic drivers of metastatic progression are less well characterized. This review describes the known molecular pathways of cutaneous and uveal melanoma progression, highlights recently identified pathways and mediators of metastasis, and touches on the influence of the tumor microenvironment on metastatic progression and treatment resistance. While targeted therapies and immune checkpoint blockade have significantly aided in the treatment of advanced disease, acquired drug resistance remains an unfortunately common problem, and there is still a great need to identify potential prognostic markers and novel therapeutic targets to aid in such cases.

Keywords: BRAF; MAPK; genomics; melanoma; metastasis; oncogenesis; pathways; transcriptomics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Illustration of pathway components involved in melanoma progression. Orange indicates the protein is silenced, green indicates upregulation, and pink indicates upregulation or downregulation during progression. Gene written in red are implicated to have importance in melanoma metastasis.
Figure 2
Figure 2
Proposed model of progression to metastasis for cutaneous and uveal melanoma.
See this image and copyright information in PMC

References

    1. Elder D.E., Bastian B.C., Cree I.A., Massi D., Scolyer R.A. The 2018 World Health Organization Classification of Cutaneous, Mucosal, and Uveal Melanoma: Detailed Analysis of 9 Distinct Subtypes Defined by Their Evolutionary Pathway. Arch. Pathol. Lab. Med. 2020;144:500–522. doi: 10.5858/arpa.2019-0561-RA. - DOI - PubMed
    1. Lawrence M.S., Stojanov P., Polak P., Kryukov G.V., Cibulskis K., Sivachenko A., Carter S.L., Stewart C., Mermel C.H., Roberts S.A., et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214–218. doi: 10.1038/nature12213. - DOI - PMC - PubMed
    1. Hodis E., Watson I.R., Kryukov G.V., Arold S.T., Imielinski M., Theurillat J.-P., Nickerson E., Auclair D., Li L., Place C., et al. A Landscape of Driver Mutations in Melanoma. Cell. 2012;150:251–263. doi: 10.1016/j.cell.2012.06.024. - DOI - PMC - PubMed
    1. Harris R.S. Cancer mutation signatures, DNA damage mechanisms, and potential clinical implications. Genome Med. 2013;5:87. doi: 10.1186/gm490. - DOI - PMC - PubMed
    1. Turner N., Ware O., Bosenberg M. Genetics of metastasis: Melanoma and other cancers. Clin. Exp. Metastasis. 2018;35:379–391. doi: 10.1007/s10585-018-9893-y. - DOI - PubMed