Related Experiment Video
Updated: Feb 24, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours
Koichiro Kajiura1, Hiromitsu Takizawa2, Yuki Morimoto3
1Department of Thoracic, Endocrine and Oncological Surgery, Graduate School of Biomedical Sciences, Tokushima University Graduate School, Tokushima city 770-8503, Japan; Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University Graduate School, Tokushima city 770-8503, Japan.
Objectives:
Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy.
Materials And Methods:
Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry.
Results:
We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation.
Conclusions:
RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET.
Insights
Aberrant methylation of the RASSF1A gene is a key epigenetic event in thymic neuroendocrine tumors (NETs). This finding suggests RASSF1A could be a potential therapeutic target for NETs.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Aberrant promoter CpG island (CGI) methylation is a common epigenetic mechanism in cancer.
- Thymic tumours, though rare, require detailed epigenetic profiling for therapeutic insights.
Purpose of the Study:
- To identify potential epigenetic therapeutic targets for thymic neuroendocrine tumours (NETs).
- To investigate the methylation patterns of tumour suppressor genes in thymic epithelial tumours (TETs).
Main Methods:
- Genome-wide screening for CGI methylation in NET, thymic carcinoma, and B3 thymoma samples.
- Validation of methylation status using pyrosequencing.
- Analysis of gene expression via quantitative PCR and immunohistochemistry.
Main Results:
- A novel gene, RASSF1A, showed strong CGI hypermethylation specifically in NET samples.
- Hypermethylation of RASSF1A was confirmed in NET and inversely correlated with tumour grade.
- RASSF1A mRNA and protein expression were negatively regulated by DNA methylation.
Conclusions:
- RASSF1A functions as a tumour suppressor gene epigenetically dysregulated in NET.
- This study is the first to report RASSF1A hypermethylation in TETs.
- RASSF1A presents a potential epigenetic therapeutic target for thymic NETs.
More Related Videos
11:11Desthiobiotin-Streptavidin-Affinity Mediated Purification of RNA-Interacting Proteins in Mesothelioma Cells
Published on: April 25, 2018
09:33Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
Related Concept Videos
Epigenetic Regulation
Epigenetic Regulation
X-chromosome...
Abnormal Proliferation
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
MicroRNAs
MicroRNAs