Evidence map›Paper›PMID 12692057›Full record

ArticleGut2003

Mutations of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma.

A Tannapfel, F Sommerer, M Benicke, A Katalinic, D Uhlmann, H Witzigmann, J Hauss, C Wittekind

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gut, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
164citing papers in PubMed, 1 pooled it
13.4field-weighted citation impact, top 1% 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

164 citing papers in PubMed, 1 synthesis or guideline pooled it, 341 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Binimetinib plus Gemcitabine and Cisplatin Phase I/II Trial in Patients with Advanced Biliary Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
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  9. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2011
    Trial
  10. Phase II study of the mitogen-activated protein kinase 1/2 inhibitor selumetinib in patients with advanced hepatocellular carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2011
    Trial
  11. Trial
  12. Article
  13. Review
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  19. Article
  20. Biliary tract cancers: advances in diagnostic and management.Exploration of targeted anti-tumor therapy · 2025
    Review

104 more citing papers are in PubMed but not listed here.

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

8 authors at 3 institutions in 1 country.

A TannapfelInstitute of Pathology, University of Leipzig, Germany. tana@medizin.uni-leipzig.de
F Sommerer
M Benicke
A Katalinic
D Uhlmann
H Witzigmann
J Hauss
C Wittekind
Leipzig University · DELeipzig University of Applied Sciences · DEUniversity of Lübeck · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe Raf/MEK/ERK (mitogen activated protein kinase-MAPK) signal transduction cascade is an important mediator of a number of cellular fates, including growth, proliferation, and survival. The BRAF gene, one of the human isoforms of RAF, is activated by oncogenic Ras, leading to cooperative effects in cells responding to growth factor signals.

aimsThe aim of this study was to elucidate a possible function of BRAF in liver tumours.

methodsMutations of BRAF and KRAS were evaluated in 25 hepatocellular carcinomas (HCC) and in 69 cholangiocarcinomas (CC) by direct DNA sequencing analyses after microdissection. The presence of active intermediates of the MAPK pathway was assessed immunohistochemically. The results obtained were correlated with histopathological variables and patient survival.

resultsActivating BRAF missense mutations were identified in 15/69 CC (22%) and in one case of tumour surrounding liver. KRAS mutations were found in 31 of 69 (45%) CC examined and in two cases of tumour surrounding non-neoplastic liver tissue. In HCC, neither BRAF nor KRAS mutations were detected. All 31 CC with KRAS mutations had an intact BRAF gene. We failed to observe a correlation between BRAF or KRAS mutations and histopathological factors or prognosis of patients.

conclusionsOur data indicate that BRAF gene mutations are a relatively common event in CC but not in HCC. Disruption of the Raf/MEK/ERK (MAPK) kinase pathway, either by RAS or BRAF mutation, was detected in approximately 62% of all CC and is therefore one of the most frequent defects in cholangiocellular carcinogenesis.

Indexed as

Bile Ducts, IntrahepaticBase SequenceBile Duct NeoplasmsCarcinoma, HepatocellularCholangiocarcinomaDNA, NeoplasmExonsGenes, rasHepatectomyHumansImmunohistochemistryLiverLiver NeoplasmsMitogen-Activated Protein KinasesMutation, MissenseProto-Oncogene Proteins B-rafBRAF protein, humanDNA, NeoplasmMitogen-Activated Protein KinasesProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-raf

Identifiers

PMID12692057
PMCPMC1773624
OpenAlexW1989145928

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.