ArticleGut2000
Frequency of p16(INK4A) alterations and K-ras mutations in intrahepatic cholangiocarcinoma of the liver.
Article in Gut, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 192 citations in OpenAlex.
- Genomic and genetic characterization of cholangiocarcinoma identifies therapeutic targets for tyrosine kinase inhibitors.Gastroenterology · 2012Pooled it
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- A New Staining Method Using Methionyl-tRNA Synthetase 1 Antibody for Endoscopic Ultrasound-Guided Fine-Needle Aspiration Cytology of Pancreatic Cancer.Diagnostics (Basel, Switzerland) · 2025Article
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- Intraductal papillary neoplasm of the bile duct: Cytomorphologic and molecular features.Cancer cytopathology · 2023Article
- DNA methylation in cell plasticity and malignant transformation in liver diseases.Pharmacology & therapeutics · 2023Review
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- Integrated Bioinformatic Analysis IdentifiesDisease markers · 2022Article
- Intrahepatic Cholangiocarcinoma: A Summative Review of Biomarkers and Targeted Therapies.Cancers · 2021Review
- Cholangiocarcinoma and liver transplantation: What we know so far?World journal of gastrointestinal pathophysiology · 2021Review
- Oncogenic KRAS-expressing organoids with biliary epithelial stem cell properties give rise to biliary tract cancer in mice.Cancer science · 2021Article
- Optimal tissue sampling during ERCP and emerging molecular techniques for the differentiation of benign and malignant biliary strictures.Therapeutic advances in gastroenterology · 2021Review
- Detecting cholangiocarcinoma in patients with primary sclerosing cholangitis - The promise of DNA methylation and molecular biomarkers.JHEP reports : innovation in hepatology · 2020Review
- In Vivo Models for Cholangiocarcinoma-What Can We Learn for Human Disease?International journal of molecular sciences · 2020Review
- Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine.JHEP reports : innovation in hepatology · 2020Article
- mTOR Inhibitors in Advanced Biliary Tract Cancers.International journal of molecular sciences · 2019Review
- Emerging role of precision medicine in biliary tract cancers.NPJ precision oncology · 2018Review
- Elevated AQP1 Expression Is Associated With Unfavorable Oncologic Outcome in Patients With Hilar Cholangiocarcinoma.Technology in cancer research & treatment · 2017Article
- Signaling pathways as therapeutic targets in biliary tract cancer.Expert opinion on therapeutic targets · 2017Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInactivation of the tumour suppressor gene p16 (CDKN2/MTS-1/INK4A) and K-ras mutations are among the most frequent genetic alterations in human malignancies.
aimsTo investigate the tumour suppressor gene p16 and its possible association with K-ras mutations in intrahepatic cholangiocarcinomas of the liver.
methodsThe status of p16 was evaluated in 41 cholangiocarcinomas by methylation specific polymerase chain reaction, microsatellite analysis, DNA sequencing, and immunohistochemical staining. K-ras mutations were determined by direct DNA sequencing analyses after microdissection. The results obtained were correlated with histopathological variables and patient survival.
resultsHypermethylation of the 5' CpG island of the p16 gene was found in 34 of 41 (83%) carcinomas. Homozygous deletion at the p16 region was present in two (5%), and loss of heterozygosity (LOH) in eight cases (20%). We failed to detect p16 gene missense mutations. K-ras mutations were found in 22 of 41 (54%) cholangiocarcinomas and in two cases of tumour surrounding non-neoplastic liver tissue. All 22 cancers with K-ras mutations also exhibited methylated p16. We failed to observe a correlation between K-ras or p16 status and histopathological factors or prognosis of patients.
conclusionThese data suggest that inactivation of the p16 gene is a frequent event in cholangiocarcinoma. The most common somatic alteration is promotor methylation of the p16 gene which is closely associated with K-ras mutations. We failed to establish p16 or K-ras status as independent prognostic factors in these tumours.
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