Evidence map›Paper›PMID 25065594›Full record

ArticleOncogene2015

Differential in vivo tumorigenicity of diverse KRAS mutations in vertebrate pancreas: A comprehensive survey.

J T Park, N Johnson, S Liu, M Levesque, Y J Wang, H Ho, D Huso, A Maitra, M J Parsons, J D Prescott and 1 more

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.2field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 37 citations in OpenAlex.

  1. Trial
  2. Article
  3. Molecular origin, discovery, validation and application of neoantigens.Asian journal of pharmaceutical sciences · 2026
    Review
  4. Article
  5. Review
  6. Recent Advances in Covalent Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2023
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Gastroenterology research and practice · 2020
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

J T ParkDepartment of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
N JohnsonDepartment of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
S LiuDepartment of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
M LevesqueDepartment of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Y J WangGraduate Program in Human Genetics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
H HoDepartment of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
D HusoDepartment of Molecular & Comparative Pathobiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
A MaitraDepartment of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
M J Parsons1] Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA [2] Graduate Program in Human Genetics, Johns Hopkins Medical Institutions, Baltimore, MD, USA [3] Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
J D PrescottDepartment of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
S D Leach1] Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA [2] Graduate Program in Human Genetics, Johns Hopkins Medical Institutions, Baltimore, MD, USA [3] Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Johns Hopkins University · US

Funding

Predoctoral Training Program in Human GeneticsT32GM007814 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 1985 to 2021
$10.6M
Zebrafish CoreP01CA134292 · NCI · JOHNS HOPKINS UNIVERSITY · PI LEACH, STEVEN D · 2009 to 2013
$7.4M
Identifying the Progenitors Responsible for Beta Cell Regeneration in ZebrafishR01DK080730 · NIDDK · UNIVERSITY OF CALIFORNIA-IRVINE · PI PARSONS, MICHAEL J · 2008 to 2021
$4.5M
NCI NIH HHS P01 CA134292NIDDK NIH HHS R01 DK080730NIGMS NIH HHS T32 GM007814
6 · The paper itself

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.

Indexed as

AnimalsCell Transformation, NeoplasticEpitheliumGene Expression Regulation, NeoplasticHumansMitogen-Activated Protein Kinase KinasesMutationPancreasPancreatic NeoplasmsProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)ras ProteinsVertebratesZebrafishKRAS protein, humanMAS1 protein, humanMitogen-Activated Protein Kinase KinasesProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)ras Proteins

Identifiers

PMID25065594
PMCPMC4836617
OpenAlexW2070876945

What OpenQuestion holds

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Registered trials

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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.