ArticleThe American journal of pathology2002
Aberrant methylation of preproenkephalin and p16 genes in pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma.
Article in The American journal of pathology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses that pooled it.
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Who cites it
89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 223 citations in OpenAlex.
- Prognostic and clinicopathological value of p16 protein aberrant expression in colorectal cancer: A PRISMA-compliant Meta-analysis.Medicine · 2018Pooled it
- Clinicopathological Significance of CDKN2A Promoter Hypermethylation Frequency with Pancreatic Cancer.Scientific reports · 2015Pooled it
- Nutrition-Based Paternal Influence on Gynecological Diseases in Female Offspring via Epigenetic Mechanisms.Nutrients · 2025Review
- Advances in pancreatic cancer epigenetics: From the mechanism to the clinic.World journal of gastrointestinal oncology · 2025Review
- From precursor to cancer: decoding the intrinsic and extrinsic pathways of pancreatic intraepithelial neoplasia progression.Carcinogenesis · 2024Review
- Selective epigenetic alterations in RNF43 in pancreatic exocrine cells from high-fat-diet-induced obese mice; implications for pancreatic cancer.BMC research notes · 2024Article
- Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression.Cancers · 2024Review
- p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker?Pathogens (Basel, Switzerland) · 2024Review
- The role of diagnostic, prognostic, and predictive biomarkers in the management of early pancreatic cancer.Journal of cancer research and clinical oncology · 2023Review
- Diagnosing and monitoring pancreatic cancer through cell-free DNA methylation: progress and prospects.Biomarker research · 2023Review
- Deoxyribonucleic acid methylation driven aberrations in pancreatic cancer-related pathways.World journal of gastrointestinal oncology · 2023Review
- Senescence program and its reprogramming in pancreatic premalignancy.Cell death & disease · 2023Review
- Bioinformatics-based construction of prognosis-related methylation prediction model for pancreatic cancer patients and its application value.Frontiers in pharmacology · 2023Article
- Epigenetic reprogramming in pancreatic premalignancy and clinical implications.Frontiers in oncology · 2023Review
- Identification and validation of methylated PENK gene for early detection of bladder cancer using urine DNA.BMC cancer · 2022Article
- Pancreatic Cancer: Pathogenesis, Screening, Diagnosis, and Treatment.Gastroenterology · 2022Review
- Oncogenomic Changes in Pancreatic Cancer and Their Detection in Stool.Biomolecules · 2022Review
- Prevalence of HPV Infection and p16Vaccines · 2022Article
- Review
- Mutations in key driver genes of pancreatic cancer: molecularly targeted therapies and other clinical implications.Acta pharmacologica Sinica · 2021Review
29 more citing papers are in PubMed but not listed here.
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9 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic intraductal neoplasia (PanIN) is thought to be the precursor to infiltrating pancreatic ductal adenocarcinoma. We have previously shown that the preproenkephalin (ppENK) and p16 genes are aberrantly methylated in pancreatic adenocarcinoma. In this study we define the methylation status of the ppENK and p16 genes in various grades of PanINs. One hundred seventy-four samples (28 nonneoplastic pancreatic epithelia, 7 reactive epithelia, 29 PanIN-1A, 48 PanIN-1B, 27 PanIN-2, 14 PanIN-3, 15 invasive ductal adenocarcinomas, and 6 miscellaneous pancreatic neoplasms) were microdissected from 29 formalin-fixed paraffin-embedded surgically resected pancreata, and were analyzed by methylation-specific polymerase chain reaction. Fourteen of 15 (93.3%) invasive pancreatic ductal adenocarcinomas showed methylation of the ppENK gene and 4 of 15 (26.7%) showed methylation of the p16 gene. Nonneoplastic pancreatic epithelia did not harbor methylation of either gene. The prevalence of methylation of the ppENK gene increased significantly with increasing PanIN grade. A similar nonsignificant trend was noted for p16 methylation. Aberrant methylation of the ppENK gene was found in 7.7% of PanIN-1A, 7.3% of PanIN-1B, 22.7% of PanIN-2, and 46.2% of PanIN-3. Aberrant methylation of the p16 gene was found in 12% of PanIN-1A, 2.6% of PanIN-1B, 4.5% of PanIN-2, and 21.4% of PanIN-3. All but one of the PanINs from the 14 pancreata without pancreatic carcinoma was unmethylated with respect to either the p16 or ppENK gene. Our results suggest that methylation-related inactivation of the ppENK and p16 genes is an intermediate or late event during pancreatic carcinogenesis. Because aberrant methylation of ppENK or p16 was more often detected in similar grade PanINs from patients with pancreatic carcinoma than in those with other pancreatic diseases, it may be a useful indicator of the potential malignancy of epithelial cells of the pancreas.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.