SynthesisJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2013
CDKN2A/p16 inactivation mechanisms and their relationship to smoke exposure and molecular features in non-small-cell lung cancer.
Synthesis in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- CDKN2A methylation in esophageal cancer: a meta-analysis.Oncotarget · 2017Pooled it
- Genetics and Molecular Mechanisms in Oral Squamous Cell Carcinoma: A Narrative Review.Medicina (Kaunas, Lithuania) · 2026Review
- Molecular Links Between Smoking, COPD, and Lung Cancer: A DNA Methylation Perspective.Cancers · 2026Article
- Article
- Tumor suppressor genes and KRAS G12C inhibitor resistance in non-small cell lung cancer.iScience · 2026Review
- The microbiome and its impact on the epigenome in cancer.Frontiers in epigenetics and epigenomics · 2026Review
- Primary Pulmonary NUT Carcinoma: A Case Illustration of Therapeutic Challenges and Review of Emerging Targeted Therapies.Case reports in oncological medicine · 2026Article
- Silencing SOX2OT reduces viability and migration in lung cancer cells via lncRNA and protein regulation.Medical oncology (Northwood, London, England) · 2025Article
- Differential Response and Resistance to KRAS-Targeted Therapy.Molecular carcinogenesis · 2025Review
- SAM486A-induced inhibition of AMD1: metabolic and epigenetic implications in non-small cell lung cancer cells.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- DNA methylation heterogeneity correlates with field cancerization and prognosis in lung adenocarcinoma patients.Clinical epigenetics · 2025Article
- Molecular mechanism of genetic, epigenetic, and metabolic alteration in lung cancer.Medical oncology (Northwood, London, England) · 2025Review
- Genomic characteristics of PD-L1-Induced resistance to EGFR-TKIs in lung adenocarcinoma.Future oncology (London, England) · 2024Article
- The Potential Association of CDKN2A and Ki-67 Proteins in View of the Selected Characteristics of Patients with Head and Neck Squamous Cell Carcinoma.Current issues in molecular biology · 2024Article
- Cuproptosis in cancer: biological implications and therapeutic opportunities.Cellular & molecular biology letters · 2024Review
- Ganglioglioma with anaplastic/high-grade transformation: Histopathologic, molecular, and epigenetic characterization of 3 cases.Journal of neuropathology and experimental neurology · 2024Article
- Epigenetic changes driven by environmental pollutants in lung carcinogenesis: a comprehensive review.Frontiers in public health · 2024Review
- Comparative analysis of PD-L1 expression and molecular alterations in primary versus metastatic lung adenocarcinoma: a real-world study in China.Frontiers in oncology · 2024Article
- Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner.Open life sciences · 2024Article
- Molecular profiles of different PD-L1 expression in patients with esophageal squamous cell carcinoma.Cancer biology & therapy · 2023Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 8 institutions in 3 countries.
Funding
Abstract
introductionCDKN2A (p16) inactivation is common in lung cancer and occurs via homozygous deletions, methylation of promoter region, or point mutations. Although p16 promoter methylation has been linked to KRAS mutation and smoking, the associations between p16 inactivation mechanisms and other common genetic mutations and smoking status are still controversial or unknown.
methodsWe determined all three p16 inactivation mechanisms with the use of multiple methodologies for genomic status, methylation, RNA, and protein expression, and correlated them with EGFR, KRAS, STK11 mutations and smoking status in 40 cell lines and 45 tumor samples of primary non-small-cell lung carcinoma. We also performed meta-analyses to investigate the impact of smoke exposure on p16 inactivation.
resultsp16 inactivation was the major mechanism of RB pathway perturbation in non-small-cell lung carcinoma, with homozygous deletion being the most frequent method, followed by methylation and the rarer point mutations. Inactivating mechanisms were tightly correlated with loss of mRNA and protein expression. p16 inactivation occurred at comparable frequencies regardless of mutational status of EGFR, KRAS, and STK11, however, the major inactivation mechanism of p16 varied. p16 methylation was linked to KRAS mutation but was mutually exclusive with EGFR mutation. Cell lines and tumor samples demonstrated similar results. Our meta-analyses confirmed a modest positive association between p16 promoter methylation and smoking.
conclusionOur results confirm that all the inactivation mechanisms are truly associated with loss of gene product and identify specific associations between p16 inactivation mechanisms and other genetic changes and smoking status.
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