Evidence map›Paper›PMID 24676216›Full record

ArticlePLoS genetics2014

Changes in colorectal carcinoma genomes under anti-EGFR therapy identified by whole-genome plasma DNA sequencing.

Sumitra Mohan, Ellen Heitzer, Peter Ulz, Ingrid Lafer, Sigurd Lax, Martina Auer, Martin Pichler, Armin Gerger, Florian Eisner, Gerald Hoefler and 3 more

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

Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 3 pooled it
11.2field-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

84 citing papers in PubMed, 3 syntheses or guidelines pooled it, 177 citations in OpenAlex.

  1. Pooled it
  2. Circulating Cell-Free DNA and Colorectal Cancer: A Systematic Review.International journal of molecular sciences · 2018
    Pooled it
  3. Pooled it
  4. Trial
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Liquid biopsy-based early tumor and minimal residual disease detectionMedizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2023
    Article
  12. Review
  13. Review
  14. Review
  15. Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review

24 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

13 authors at 1 institution in 1 country.

Sumitra MohanInstitute of Human Genetics, Medical University of Graz, Graz, Austria.
Ellen HeitzerInstitute of Human Genetics, Medical University of Graz, Graz, Austria.
Peter UlzInstitute of Human Genetics, Medical University of Graz, Graz, Austria.
Ingrid LaferInstitute of Human Genetics, Medical University of Graz, Graz, Austria.
Sigurd LaxDepartment of Pathology, General Hospital Graz West, Graz, Austria.
Martina AuerInstitute of Human Genetics, Medical University of Graz, Graz, Austria.
Martin PichlerDivision of Oncology, Medical University of Graz, Graz, Austria.
Armin GergerDivision of Oncology, Medical University of Graz, Graz, Austria.
Florian EisnerDivision of Oncology, Medical University of Graz, Graz, Austria.
Gerald HoeflerInstitute of Pathology, Medical University of Graz, Graz, Austria.
Thomas BauernhoferDivision of Oncology, Medical University of Graz, Graz, Austria.
Jochen B GeiglInstitute of Human Genetics, Medical University of Graz, Graz, Austria.
Michael R SpeicherInstitute of Human Genetics, Medical University of Graz, Graz, Austria.
Medical University of Graz · AT

Funding

Austrian Science Fund FWF P 23284Austrian Science Fund FWF W 1226
6 · The paper itself

Abstract

Monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR), such as cetuximab and panitumumab, have evolved to important therapeutic options in metastatic colorectal cancer (CRC). However, almost all patients with clinical response to anti-EGFR therapies show disease progression within a few months and little is known about mechanism and timing of resistance evolution. Here we analyzed plasma DNA from ten patients treated with anti-EGFR therapy by whole genome sequencing (plasma-Seq) and ultra-sensitive deep sequencing of genes associated with resistance to anti-EGFR treatment such as KRAS, BRAF, PIK3CA, and EGFR. Surprisingly, we observed that the development of resistance to anti-EGFR therapies was associated with acquired gains of KRAS in four patients (40%), which occurred either as novel focal amplifications (n = 3) or as high level polysomy of 12p (n = 1). In addition, we observed focal amplifications of other genes recently shown to be involved in acquired resistance to anti-EGFR therapies, such as MET (n = 2) and ERBB2 (n = 1). Overrepresentation of the EGFR gene was associated with a good initial anti-EGFR efficacy. Overall, we identified predictive biomarkers associated with anti-EGFR efficacy in seven patients (70%), which correlated well with treatment response. In contrast, ultra-sensitive deep sequencing of KRAS, BRAF, PIK3CA, and EGFR did not reveal the occurrence of novel, acquired mutations. Thus, plasma-Seq enables the identification of novel mutant clones and may therefore facilitate early adjustments of therapies that may delay or prevent disease progression.

Indexed as

AgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBiomarkers, TumorCetuximabColorectal NeoplasmsDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesErbB ReceptorsFemaleGenome, HumanHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBiomarkers, TumorCetuximabEGFR protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesErbB ReceptorsMET protein, humanPanitumumabProto-Oncogene Proteins c-met

Identifiers

PMID24676216
PMCPMC3967949
OpenAlexW2035022458

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.