Methylation of nonessential genes in cutaneous melanoma - Rule Out hypothesis.

Autor:	Gorlov IP; Department of Medicine, Baylor College of Medicine, Houston, Texas., Conway K; Department of Dermatology, University of North Carolina.; Department of Epidemiology.; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Edmiston SN; Department of Dermatology, University of North Carolina.; Department of Epidemiology.; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Parrish EA; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.; Department of Applied Mathematics and Statistics, State University of New York, Stony Brook., Hao H; Department of Dermatology, University of North Carolina., Amos CI; Department of Medicine, Baylor College of Medicine, Houston, Texas., Tsavachidis S; Department of Medicine, Baylor College of Medicine, Houston, Texas., Gorlova OY; Department of Medicine, Baylor College of Medicine, Houston, Texas., Begg C; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York., Hernando E; Department of Pathology, New York University School of Medicine, New York., Cheng C; Department of Medicine, Baylor College of Medicine, Houston, Texas., Shen R; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York., Orlow I; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York., Luo L; Department of Internal Medicine, University of New Mexico, Albuquerque, New Maxico., Ernstoff MS; Roswell Park Comprehensive Cancer Center, Elm and Carlton, Buffalo., Kuan PF; Department of Applied Mathematics and Statistics, State University of New York, Stony Brook and., Ollila DW; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.; Department of Surgery, University of North Carolina, Chapel Hill, North Carolina, USA., Tsai YS; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Berwick M; Department of Internal Medicine, University of New Mexico, Albuquerque, New Maxico., Thomas NE; Department of Dermatology, University of North Carolina.; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Jazyk:	angličtina
Zdroj:	Melanoma research [Melanoma Res] 2023 Jun 01; Vol. 33 (3), pp. 163-172. Date of Electronic Publication: 2023 Feb 20.
DOI:	10.1097/CMR.0000000000000881
Abstrakt:	Differential methylation plays an important role in melanoma development and is associated with survival, progression and response to treatment. However, the mechanisms by which methylation promotes melanoma development are poorly understood. The traditional explanation of selective advantage provided by differential methylation postulates that hypermethylation of regulatory 5'-cytosine-phosphate-guanine-3' dinucleotides (CpGs) downregulates the expression of tumor suppressor genes and therefore promotes tumorigenesis. We believe that other (not necessarily alternative) explanations of the selective advantages of methylation are also possible. Here, we hypothesize that melanoma cells use methylation to shut down transcription of nonessential genes - those not required for cell survival and proliferation. Suppression of nonessential genes allows tumor cells to be more efficient in terms of energy and resource usage, providing them with a selective advantage over the tumor cells that transcribe and subsequently translate genes they do not need. We named the hypothesis the Rule Out (RO) hypothesis. The RO hypothesis predicts higher methylation of CpGs located in regulatory regions (CpG islands) of nonessential genes. It also predicts the higher methylation of regulatory CpGs linked to nonessential genes in melanomas compared to nevi and lower expression of nonessential genes in malignant (derived from melanoma) versus normal (derived from nonaffected skin) melanocytes. The analyses conducted using in-house and publicly available data found that all predictions derived from the RO hypothesis hold, providing observational support for the hypothesis. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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