Related Experiment Video
Updated: Jul 10, 2026
LINE-1 Methylation Analysis in Mesenchymal Stem Cells Treated with Osteosarcoma-Derived Extracellular Vesicles
Published on: February 1, 2020
Tumor-type specific methylation patterns of MTAP in human samples and cell lines
Luis Álvarez-Carrión1, Dalma Müller2, Manuel Pedregal3
1CANMET Research Group, Cátedra INTHEOS-START-CEU de Oncología de Precision, Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Instituto de Medicina Molecular Aplicada (IMMA), Universidad San Pablo-CEU, CEU Universities ES, Urbanización Montepríncipe, 28660, Boadilla del Monte, Spain.
Abstract:
Loss of methylthioadenosine phosphorylase creates a therapeutically dependency on PRMT5, yet current strategies select patients based only on MTAP genomic deletion. We performed an integrated analysis of DNA methylation and gene expression using TCGA, TARGET and ENCODE data to identify alternative mechanisms of MTAP inactivation. A promoter-proximal CpG site (cg25162921) showed a frequent hypermethylation and strong inverse correlation with MTAP mRNA expression across multiple tumor types and cell lines, including lung squamous cell carcinoma and glioblastoma. These findings identify promoter hypermethylation as a copy-number-independent mechanism of MTAP silencing and support epigenetic profiling evaluation in tumor samples into MTAP-based precision oncology.
Insights
Methylthioadenosine phosphorylase (MTAP) loss creates a dependency on PRMT5. This study reveals promoter hypermethylation as a key MTAP inactivation mechanism, suggesting epigenetic profiling for MTAP-based precision oncology.
Area of Science:
- Oncology
- Epigenetics
- Genomics
Background:
- Loss of methylthioadenosine phosphorylase (MTAP) creates a therapeutic dependency on PRMT5.
- Current patient selection for MTAP-targeted therapies relies solely on MTAP genomic deletion.
- Alternative mechanisms of MTAP inactivation remain underexplored.
Purpose of the Study:
- To identify alternative, copy-number-independent mechanisms of MTAP inactivation.
- To investigate the role of DNA methylation in MTAP silencing.
- To support the integration of epigenetic profiling into MTAP-based precision oncology.
Main Methods:
- Integrated analysis of DNA methylation and gene expression data.
- Utilized datasets from TCGA, TARGET, and ENCODE.
- Focused on promoter-proximal CpG site (cg25162921) methylation and MTAP mRNA expression correlation.
Main Results:
- Identified frequent hypermethylation at promoter-proximal CpG site cg25162921.
- Demonstrated a strong inverse correlation between cg25162921 hypermethylation and MTAP mRNA expression.
- Observed this epigenetic silencing mechanism across multiple tumor types and cell lines, including lung squamous cell carcinoma and glioblastoma.
Conclusions:
- Promoter hypermethylation is a significant copy-number-independent mechanism for MTAP inactivation.
- Epigenetic profiling of tumor samples can identify alternative MTAP silencing pathways.
- Findings support the evaluation of epigenetic markers for patient stratification in MTAP-targeted therapies.
