Genetic and Genomic Pathways of Melanoma Development, Invasion and Metastasis

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2021 Oct 23

PMID 34680938

Citations 9

Authors

Jyoti Motwani

Michael R Eccles

Affiliations

Soon will be listed here.

Abstract

Melanoma is a serious form of skin cancer that accounts for 80% of skin cancer deaths. Recent studies have suggested that melanoma invasiveness is attributed to phenotype switching, which is a reversible type of cell behaviour with similarities to epithelial to mesenchymal transition. Phenotype switching in melanoma is reported to be independent of genetic alterations, whereas changes in gene transcription, and epigenetic alterations have been associated with invasiveness in melanoma cell lines. Here, we review mutational, transcriptional, and epigenomic alterations that contribute to tumour heterogeneity in melanoma, and their potential to drive melanoma invasion and metastasis. We also discuss three models that are hypothesized to contribute towards aspects of tumour heterogeneity and tumour progression in melanoma, namely the clonal evolution model, the cancer stem cell model, and the phenotype switching model. We discuss the merits and disadvantages of each model in explaining tumour heterogeneity in melanoma, as a precursor to invasion and metastasis.

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References

Lee Y, Shin H, Choi W, Ahn S, Kim W . Characterization of human SMARCE1r high-mobility-group protein. Biochim Biophys Acta. 2002; 1574(3):269-76. DOI: 10.1016/s0167-4781(01)00373-6. View

Zhu Z, Liu W, Gotlieb V . The rapidly evolving therapies for advanced melanoma--Towards immunotherapy, molecular targeted therapy, and beyond. Crit Rev Oncol Hematol. 2015; 99:91-9. DOI: 10.1016/j.critrevonc.2015.12.002. View

Huang F, Hodis E, Xu M, Kryukov G, Chin L, Garraway L . Highly recurrent TERT promoter mutations in human melanoma. Science. 2013; 339(6122):957-9. PMC: 4423787. DOI: 10.1126/science.1229259. View

Ben-Chetrit N, Chetrit D, Russell R, Korner C, Mancini M, Abdul-Hai A . Synaptojanin 2 is a druggable mediator of metastasis and the gene is overexpressed and amplified in breast cancer. Sci Signal. 2015; 8(360):ra7. DOI: 10.1126/scisignal.2005537. View

Motwani J, Rodger E, Stockwell P, Baguley B, Macaulay E, Eccles M . Genome-wide DNA methylation and RNA expression differences correlate with invasiveness in melanoma cell lines. Epigenomics. 2021; 13(8):577-598. DOI: 10.2217/epi-2020-0440. View

Hunter T, Pines J . Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell. 1994; 79(4):573-82. DOI: 10.1016/0092-8674(94)90543-6. View

Mani S, Guo W, Liao M, Eaton E, Ayyanan A, Zhou A . The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133(4):704-15. PMC: 2728032. DOI: 10.1016/j.cell.2008.03.027. View

Goydos J, Mann B, Kim H, Gabriel E, Alsina J, Germino F . Detection of B-RAF and N-RAS mutations in human melanoma. J Am Coll Surg. 2005; 200(3):362-70. DOI: 10.1016/j.jamcollsurg.2004.10.032. View

Hill V, Gartner J, Samuels Y, Goldstein A . The genetics of melanoma: recent advances. Annu Rev Genomics Hum Genet. 2013; 14:257-79. DOI: 10.1146/annurev-genom-091212-153429. View

10.

Quintana E, Shackleton M, Sabel M, Fullen D, Johnson T, Morrison S . Efficient tumour formation by single human melanoma cells. Nature. 2008; 456(7222):593-8. PMC: 2597380. DOI: 10.1038/nature07567. View

11.

Sharma B, Manglik V, Elias E . Immuno-expression of human melanoma stem cell markers in tissues at different stages of the disease. J Surg Res. 2010; 163(1):e11-5. DOI: 10.1016/j.jss.2010.03.043. View

12.

Kuznetsov J, Aguero T, Owens D, Kurtenbach S, Field M, Durante M . BAP1 regulates epigenetic switch from pluripotency to differentiation in developmental lineages giving rise to BAP1-mutant cancers. Sci Adv. 2019; 5(9):eaax1738. PMC: 6750916. DOI: 10.1126/sciadv.aax1738. View

13.

Ingber D . Can cancer be reversed by engineering the tumor microenvironment?. Semin Cancer Biol. 2008; 18(5):356-64. PMC: 2570051. DOI: 10.1016/j.semcancer.2008.03.016. View

14.

He S, Li C, Slobbe L, Glover A, Marshall E, Baguley B . PAX3 knockdown in metastatic melanoma cell lines does not reduce MITF expression. Melanoma Res. 2010; 21(1):24-34. DOI: 10.1097/CMR.0b013e328341c7e0. View

15.

Eisterer W, Jiang X, Christ O, Glimm H, Lee K, Pang E . Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a model of the human disease. Leukemia. 2005; 19(3):435-41. DOI: 10.1038/sj.leu.2403649. View

16.

Van Raamsdonk C, Griewank K, Crosby M, Garrido M, Vemula S, Wiesner T . Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010; 363(23):2191-9. PMC: 3107972. DOI: 10.1056/NEJMoa1000584. View

17.

Van Allen E, Miao D, Schilling B, Shukla S, Blank C, Zimmer L . Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2015; 350(6257):207-211. PMC: 5054517. DOI: 10.1126/science.aad0095. View

18.

Huang F, Santinon F, Flores Gonzalez R, del Rincon S . Melanoma Plasticity: Promoter of Metastasis and Resistance to Therapy. Front Oncol. 2021; 11:756001. PMC: 8481945. DOI: 10.3389/fonc.2021.756001. View

19.

Raimondi S, Sera F, Gandini S, Iodice S, Caini S, Maisonneuve P . MC1R variants, melanoma and red hair color phenotype: a meta-analysis. Int J Cancer. 2008; 122(12):2753-60. DOI: 10.1002/ijc.23396. View

20.

Emmons M, Faiao-Flores F, Sharma R, Thapa R, Messina J, Becker J . HDAC8 Regulates a Stress Response Pathway in Melanoma to Mediate Escape from BRAF Inhibitor Therapy. Cancer Res. 2019; 79(11):2947-2961. PMC: 6548652. DOI: 10.1158/0008-5472.CAN-19-0040. View