Evidence map›Paper›PMID 23599150›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2013

A subset of gastrointestinal stromal tumors previously regarded as wild-type tumors carries somatic activating mutations in KIT exon 8 (p.D419del).

Sebastian Huss, Helen Künstlinger, Eva Wardelmann, Michaela A Kleine, Elke Binot, Sabine Merkelbach-Bruse, Thomas Rüdiger, Jens Mittler, Wolfgang Hartmann, Reinhard Büttner and 1 more

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

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

28 citing papers in PubMed, 58 citations in OpenAlex.

  1. Review
  2. Article
  3. [Gastrointestinal stromal tumors : Where do we stand?]Pathologie (Heidelberg, Germany) · 2024
    Review
  4. Article
  5. [Gastrointestinal stromal tumors (GIST)].Wiener medizinische Wochenschrift (1946) · 2023
    Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Mutation Status and Immunohistochemical Correlation ofBalkan journal of medical genetics : BJMG · 2021
    Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Molecular characterization and pathogenesis of gastrointestinal stromal tumor.Translational gastroenterology and hepatology · 2018
    Review
  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 3 institutions in 1 country.

Sebastian HussInstitute of Pathology, University of Cologne, Medical Center, Cologne, Germany.
Helen Künstlinger
Eva Wardelmann
Michaela A Kleine
Elke Binot
Sabine Merkelbach-Bruse
Thomas Rüdiger
Jens Mittler
Wolfgang Hartmann
Reinhard Büttner
Hans-Ulrich Schildhaus
University of Cologne · DEJohannes Gutenberg University Mainz · DEStädtisches Klinikum Karlsruhe · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

About 10-15% of gastrointestinal stromal tumors (GISTs) carry wild-type sequences in all hot spots of KIT and platelet-derived growth factor receptor alpha (PDGFRA) (wt-GISTs). These tumors are currently defined by having no mutations in exons 9, 11, 13, and 17 of the KIT gene and exons 12, 14, and 18 of the PDGFRA gene. Until now, the analysis of further exons is not recommended. However, we have previously published a report on a KIT exon 8 germline mutation, which was associated with familial GIST and mastocytosis. We therefore investigated whether KIT exon 8 mutations might also occur in sporadic GIST. We screened a cohort of 145 wt-GISTs from a total of 1351 cases from our registry for somatic mutations in KIT exon 8. Two primary GISTs with an identical exon 8 mutation (p.D419del) were detected, representing 1.4% of all the cases analyzed. Based on all GISTs from our registry, the overall frequency of KIT exon 8 mutations was 0.15%. The first tumor originating in the small bowel of a 53-year-old male patient had mostly a biphasic spindled-epithelioid pattern with a high proliferative activity (14 mitoses/50 HPF) combined with a second low proliferative spindle cell pattern (4/50 HPF). The patient developed multiple peritoneal metastases 29 months later. The second case represented a jejunal GIST in a 67-year old woman who is relapse-free under adjuvant imatinib treatment. We conclude that about 1-2% of GISTs being classified as 'wild type' so far might, in fact, carry KIT mutations in exon 8. Moreover, this mutational subtype was shown to be activating and imatinib sensitive in vitro. We therefore propose that screening for KIT exon 8 mutations should become a routine in the diagnostic work-up of GIST and that patients with an exon 8 mutation and a significant risk for tumor progression should be treated with imatinib.

Indexed as

AdolescentAgedAged, 80 and overChildDNA Mutational AnalysisExonsFemaleGastrointestinal Stromal TumorsHumansIn Situ Hybridization, FluorescenceMaleMiddle AgedMutationProto-Oncogene Proteins c-kitYoung AdultProto-Oncogene Proteins c-kit

Identifiers

PMID23599150
PMCPMC3701292
OpenAlexW2022207031

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.