ArticleHepatology (Baltimore, Md.)2018
Genomic perturbations reveal distinct regulatory networks in intrahepatic cholangiocarcinoma.
Article in Hepatology (Baltimore, Md.), 2018. 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.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- Criteria for preclinical models of cholangiocarcinoma: scientific and medical relevance.Nature reviews. Gastroenterology & hepatology · 2023Guideline
- Global patterns of mutational profiles in biliary tract cancer.Journal of hepatology · 2026Article
- Oncogene-Mechanics Axis: KRAS G12C Confers Agility Enabling Malignant Mechano-responses to Peristalsis in Colorectal Cancer.bioRxiv : the preprint server for biology · 2026Article
- Integrated Multi-Omics Profiling Identifies an Immunotherapy Vulnerable and Prognostic Associated Subtype in Cholangiocarcinoma.Liver cancer · 2026Article
- Identification of serum peptide biomarkers for cholangiocarcinoma diagnosis and staging via MALDI-TOF MS and LC-MS/MS.British journal of cancer · 2026Article
- Cholangiocarcinoma 2026: status quo, unmet needs and priorities.Nature reviews. Gastroenterology & hepatology · 2026Review
- A novel mouse model of diverse tumors derived from epithelial cells.Physiological reports · 2025Article
- Genetic, Epigenetic, and Microenvironmental Drivers of Cholangiocarcinoma.The American journal of pathology · 2025Review
- Mapping the landscape of biliary tract cancer in Europe: challenges and controversies.The Lancet regional health. Europe · 2025Review
- Molecularly redefining small bowel adenocarcinoma to accelerate precision patient care - protocol of a multicenter observational cohort biomarker study.BMC cancer · 2025Article
- Global burden and cross-country inequalities in gallbladder and biliary tract cancer (1990-2021) with projections to 2050: insights from the global burden of disease study 2021.Frontiers in medicine · 2025Article
- Targeted therapies in biliary tract cancer-when precision becomes imprecise.ESMO gastrointestinal oncology · 2024Review
- Differential isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 mutation-related landscape in intrahepatic cholangiocarcinoma.The oncologist · 2024Article
- Mutational spectrum for guiding the decision of adjuvant treatment in patients with resected biliary tract carcinoma.Cancer medicine · 2023Article
- Targeting CD44 Variant 5 with an Antibody-Drug Conjugate Is an Effective Therapeutic Strategy for Intrahepatic Cholangiocarcinoma.Cancer research · 2023Article
- Convergent genomic diversity and novel BCAA metabolism in intrahepatic cholangiocarcinoma.British journal of cancer · 2023Article
- Review
- MicroRNA-27a-3p targets FoxO signalling to induce tumour-like phenotypes in bile duct cells.Journal of hepatology · 2023Article
- Review
- Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 7 institutions in 8 countries.
Funding
Abstract
Intrahepatic cholangiocarcinoma remains a highly heterogeneous malignancy that has eluded effective patient stratification to date. The extent to which such heterogeneity can be influenced by individual driver mutations remains to be evaluated. Here, we analyzed genomic (whole-exome sequencing, targeted exome sequencing) and epigenomic data from 496 patients and used the three most recurrently mutated genes to stratify patients (IDH, KRAS, TP53, "undetermined"). Using this molecular dissection approach, each subgroup was determined to possess unique mutational signature preferences, comutation profiles, and enriched pathways. High-throughput drug repositioning in seven patient-matched cell lines, chosen to reflect the genetic alterations specific for each patient group, confirmed in silico predictions of subgroup-specific vulnerabilities linked to enriched pathways. Intriguingly, patients lacking all three mutations ("undetermined") harbored the most extensive structural alterations, while isocitrate dehydrogenase mutant tumors displayed the most extensive DNA methylome dysregulation, consistent with previous findings.
conclusionStratification of intrahepatic cholangiocarcinoma patients based on occurrence of mutations in three classifier genes (IDH, KRAS, TP53) revealed unique oncogenic programs (mutational, structural, epimutational) that influence pharmacologic response in drug repositioning protocols; this genome dissection approach highlights the potential of individual mutations to induce extensive molecular heterogeneity and could facilitate advancement of therapeutic response in this dismal disease. (Hepatology 2018).
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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.