Bona Fide Tumor Suppressor Genes Hypermethylated in Melanoma: A Narrative Review
Related Experiment Video
Updated: Oct 17, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Canan Güvenç1, Fien Neckebroeck1, Asier Antoranz2
1Department of Dermatology, University Hospitals Leuven, 3000 Leuven, Belgium.
Abstract:
Loss-of-function events in tumor suppressor genes (TSGs) contribute to the development and progression of cutaneous malignant melanoma (CMM). Epigenetic alterations are the major mechanisms of TSG inactivation, in particular, silencing by promoter CpG-island hypermethylation. TSGs are valuable tools in diagnosis and prognosis and, possibly, in future targeted therapy. The aim of this narrative review is to outline bona fide TSGs affected by promoter CpG-island hypermethylation and their functional role in the progression of CMM. We conducted a systematic literature review to identify studies providing evidence of bona fide TSGs by cell line or animal experiments. We performed a broad first search and a gene-specific second search, supplemented by reference checking. We included studies describing bona fide TSGs in CMM with promoter CpG-island hypermethylation in which inactivating mechanisms were reported. We extracted data about protein role, pathway, experiments conducted to meet the bona fide criteria and hallmarks of cancer acquired by TSG inactivation. A total of 24 studies were included, describing 24 bona fide TSGs silenced by promoter CpG-island hypermethylation in CMM. Their effect on cell proliferation, apoptosis, growth, senescence, angiogenesis, migration, invasion or metastasis is also described. These data give further insight into the role of TSGs in the progression of CMM.
Insights
Tumor suppressor genes (TSGs) silenced by promoter CpG-island hypermethylation are crucial in cutaneous malignant melanoma (CMM) progression. This review details 24 bona fide TSGs and their roles in CMM development.
Area of Science:
- Oncology
- Cancer Genetics
- Epigenetics
Background:
- Loss-of-function mutations in tumor suppressor genes (TSGs) drive cancer development.
- Epigenetic silencing, particularly promoter CpG-island hypermethylation, is a key mechanism for TSG inactivation in cutaneous malignant melanoma (CMM).
- TSGs hold potential for CMM diagnosis, prognosis, and targeted therapies.
Purpose of the Study:
- To identify and review bona fide TSGs inactivated by promoter CpG-island hypermethylation in CMM.
- To elucidate the functional roles of these TSGs in CMM progression.
- To consolidate current knowledge on epigenetic TSG silencing in melanoma.
Main Methods:
- Systematic literature review using broad and gene-specific searches.
- Inclusion of studies with experimental evidence for bona fide TSGs in CMM.
- Data extraction on protein function, pathways, experimental validation, and cancer hallmarks affected.
Main Results:
- Twenty-four bona fide TSGs silenced by promoter CpG-island hypermethylation in CMM were identified across 24 studies.
- The functional impact of these TSGs on critical cancer processes including proliferation, apoptosis, angiogenesis, migration, invasion, and metastasis was described.
- Evidence supports the role of these epigenetically silenced TSGs in driving CMM progression.
Conclusions:
- Promoter CpG-island hypermethylation is a significant mechanism for TSG inactivation in CMM.
- Inactivated TSGs play critical roles in multiple hallmarks of cancer, contributing to melanoma progression.
- Understanding these TSGs offers insights into CMM pathogenesis and potential therapeutic strategies.
Related Concept Videos
02:23Abnormal Proliferation
01:37Epigenetic Regulation
X-chromosome...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:17The Tumor Microenvironment