ArticleClinical epigenetics2021
Fibroblast growth factor (FGF), FGF receptor (FGFR), and cyclin D1 (CCND1) DNA methylation in head and neck squamous cell carcinomas is associated with transcriptional activity, gene amplification, human papillomavirus (HPV) status, and sensitivity to tyrosine kinase inhibitors.
Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- MDM2 Inhibition with Alrizomadlin (APG-115) in TP53 wild-type salivary gland cancers: a phase I clinical trial.Nature communications · 2026Trial
- Prognosis and Failure Patterns of 11q13 Amplified Local Advanced Squamous Cell Carcinoma of the Head and Neck.Cancer medicine · 2025Article
- Review
- Application of CellSearch technique in detection of peripheral blood circulating tumour cell count in patients with head and neck cancer and its association with prognosis.Oncology letters · 2025Article
- Expansion of the complex genotypic and phenotypic spectrum of FGFR2-associated neurocutaneous syndromes.Human genetics · 2024Article
- Molecular Targeting of the Fibroblast Growth Factor Receptor Pathway across Various Cancers.International journal of molecular sciences · 2024Review
- A novel intronic circular RNA circFGFR1Journal of translational medicine · 2023Article
- Review
- DNA Methylation as a Diagnostic, Prognostic, and Predictive Biomarker in Head and Neck Cancer.International journal of molecular sciences · 2023Review
- Systematic analysis of expression profiles and prognostic significance of the FGF gene family in pancreatic adenocarcinoma.Oncology letters · 2022Article
- Review
- The E6 and E7 proteins of beta3 human papillomavirus 49 can deregulate both cellular and extracellular vesicles-carried microRNAs.Infectious agents and cancer · 2022Article
- Bioinformatics analysis and validation of the critical genes associated with adamantinomatous craniopharyngioma.Frontiers in oncology · 2022Article
- Therapeutic Targeting of FGFR Signaling in Head and Neck Cancer.Cancer journal (Sudbury, Mass.)Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
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Abstract
backgroundDysregulation of fibroblast growth factor receptor (FGFR) signaling pathway has been observed in head and neck squamous cell carcinoma (HNSCC) and is a promising therapeutic target for selective tyrosine kinase inhibitors (TKIs). Potential predictive biomarkers for response to FGFR-targeted therapies are urgently needed. Understanding the epigenetic regulation of FGF pathway related genes, i.e. FGFRs, FGFs, and CCND1, could enlighten the way towards biomarker-selected FGFR-targeted therapies.
methodsWe performed DNA methylation analysis of the encoding genes FGFR1, FGFR2, FGFR3, FGFR4, FGF1-14, FGF16-23, and CCND1 at single CpG site resolution (840 CpG sites) employing The Cancer Genome Research Atlas (TCGA) HNSCC cohort comprising N = 530 tumor tissue and N = 50 normal adjacent tissue samples. We correlated DNA methylation to mRNA expression with regard to human papilloma virus (HPV) and gene amplification status. Moreover, we investigated the correlation of methylation with sensitivity to the selective FGFR inhibitors PD 173074 and AZD4547 in N = 40 HPV(-) HNSCC cell lines.
resultsWe found sequence-contextually nuanced CpG methylation patterns in concordance with epigenetically regulated genes. High methylation levels were predominantly found in the promoter flank and gene body region, while low methylation levels were present in the central promoter region for most of the analyzed CpG sites. FGFRs, FGFs, and CCND1 methylation differed significantly between tumor and normal adjacent tissue and was associated with HPV and gene amplification status. CCND1 promoter methylation correlated with CCND1 amplification. For most of the analyzed CpG sites, methylation levels correlated to mRNA expression in tumor tissue. Furthermore, we found significant correlations of DNA methylation of specific CpG sites with response to the FGFR1/3-selective inhibitors PD 173074 and AZD4547, predominantly within the transcription start site of CCND1.
conclusionsOur results suggest an epigenetic regulation of CCND1, FGFRs, and FGFs via DNA methylation in HNSCC and warrants further investigation of DNA methylation as a potential predictive biomarker for response to selective FGFR inhibitors in clinical trials.
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