ArticleOncogene2015
Differential in vivo tumorigenicity of diverse KRAS mutations in vertebrate pancreas: A comprehensive survey.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Genomic markers of panitumumab resistance including ERBB2/ HER2 in a phase II study of KRAS wild-type (wt) metastatic colorectal cancer (mCRC).Oncotarget · 2016Trial
- Baseline cellular state shapes the molecular impact of mutant Kirsten rat sarcoma viral oncogene homologue (KRAS) alleles in reconstituted pancreatic cancer cells.Molecular omics · 2026Article
- Molecular origin, discovery, validation and application of neoantigens.Asian journal of pharmaceutical sciences · 2026Review
- Liver metastasis composed of pure squamous cell carcinoma component from pancreatic pure ductal adenocarcinoma: a case report.Surgical case reports · 2023Article
- Zebrafish-based platform for emerging bio-contaminants and virus inactivation research.The Science of the total environment · 2023Review
- Recent Advances in Covalent Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Functional and biological heterogeneity of KRASScience signaling · 2022Article
- Enhanced BRAF engagement by NRAS mutants capable of promoting melanoma initiation.Nature communications · 2022Article
- Genetic Engineering of Zebrafish in Cancer Research.Cancers · 2020Review
- Mutational Mosaics of Cell-Free DNA from Pancreatic Cyst Fluids.Digestive diseases and sciences · 2020Article
- Article
- A model for RAS mutation patterns in cancers: finding the sweet spot.Nature reviews. Cancer · 2018Review
- Somatic Activating KRAS Mutations in Arteriovenous Malformations of the Brain.The New England journal of medicine · 2018Article
- A system for detecting high impact-low frequency mutations in primary tumors and metastases.Oncogene · 2018Article
- Unusually long-term responses to vemurafenib in BRAF V600E mutated colon and thyroid cancers followed by the development of rare RAS activating mutations.Cancer biology & therapy · 2018Article
- Multiplexed in vivo homology-directed repair and tumor barcoding enables parallel quantification of Kras variant oncogenicity.Nature communications · 2017Article
- Article
- KRAS Alleles: The Devil Is in the Detail.Trends in cancer · 2017Review
- Noncanonical GLI1 signaling promotes stemness features and in vivo growth in lung adenocarcinoma.Oncogene · 2017Article
- Fishing for cures: The alLURE of using zebrafish to develop precision oncology therapies.NPJ precision oncology · 2017Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Somatic activation of the KRAS proto-oncogene is evident in almost all pancreatic cancers, and appears to represent an initiating event. These mutations occur primarily at codon 12 and less frequently at codons 13 and 61. Although some studies have suggested that different KRAS mutations may have variable oncogenic properties, to date there has been no comprehensive functional comparison of multiple KRAS mutations in an in vivo vertebrate tumorigenesis system. We generated a Gal4/UAS-based zebrafish model of pancreatic tumorigenesis in which the pancreatic expression of UAS-regulated oncogenes is driven by a ptf1a:Gal4-VP16 driver line. This system allowed us to rapidly compare the ability of 12 different KRAS mutations (G12A, G12C, G12D, G12F, G12R, G12S, G12V, G13C, G13D, Q61L, Q61R and A146T) to drive pancreatic tumorigenesis in vivo. Among fish injected with one of five KRAS mutations reported in other tumor types but not in human pancreatic cancer, 2/79 (2.5%) developed pancreatic tumors, with both tumors arising in fish injected with A146T. In contrast, among fish injected with one of seven KRAS mutations known to occur in human pancreatic cancer, 22/106 (20.8%) developed pancreatic cancer. All eight tumorigenic KRAS mutations were associated with downstream MAPK/ERK pathway activation in preneoplastic pancreatic epithelium, whereas nontumorigenic mutations were not. These results suggest that the spectrum of KRAS mutations observed in human pancreatic cancer reflects selection based on variable tumorigenic capacities, including the ability to activate MAPK/ERK signaling.
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Registered trials
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.