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Updated: Jun 11, 2025
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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
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Methylation, Gene Expression, and Risk Genotypes at the TERT-CLPTM1L Locus in Cervical Cancer
Dhanya Ramachandran1, Qianqian Mao1, Dandan Liao1
1Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
Molecular Carcinogenesis
|October 1, 2024
Summary
Telomere reverse transcriptase (TERT) promoter methylation is linked to cervical cancer risk variants. Genetic variations near TERT and CLPTM1L influence gene expression, impacting cervical cancer development alongside HPV infection.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Telomerase reverse transcriptase (TERT) is frequently activated in cervical cancers.
- TERT promoter hypomethylation is a potential biomarker for cervical cancer progression.
- Genetic risk variants near TERT-CLPTM1L have been identified, but their functional mechanisms in cervical cancer are unclear.
Purpose of the Study:
- To investigate the relationship between specific CpG methylation sites in the TERT promoter and CLPTM1L, and their association with known cervical cancer risk variants.
- To determine how these genetic variants and methylation patterns influence TERT and CLPTM1L gene expression in cervical tumors.
- To explore the combined impact of genetic background, methylation, and HPV infection on cervical cancer development.
Main Methods:
- Analysis of 529 CpG sites within the TERT promoter region and 3 nearby CpG islands, plus 21 CpG sites in CLPTM1L.
- Bisulfite conversion and sequencing of DNA from 190 cervical tumor samples (BioRAIDs).
- Association analysis between methylation status, genotypes of risk variants (rs27070, rs459961), and gene expression (TERT, CLPTM1L) in tumor and independent tissue samples.
Main Results:
- Eight CpG sites in TERT intron 2 showed significant methylation association with rs27070 and rs459961 genotypes in cervical tumors.
- Hypermethylation at chr5:1289663 correlated with reduced TERT mRNA levels.
- Rare alleles of rs27070 and rs459961 were linked to lower CLPTM1L and absent TERT mRNA in HPV-negative tissues, suggesting a protective role. HPV infection increased both CLPTM1L and TERT levels.
Conclusions:
- This study establishes a link between cervical cancer risk variants, DNA methylation, and gene expression of TERT and CLPTM1L.
- Genomic background and HPV infection modulate TERT and CLPTM1L, implicating them in cervical cancer development.
- Understanding these molecular interactions provides insights into cervical cancer pathogenesis and potential therapeutic targets.
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