Evidence map›Paper›PMID 23730412›Full record

ArticleTranslational oncology2013

Circulating Cell-Free DNA from Colorectal Cancer Patients May Reveal High KRAS or BRAF Mutation Load.

Florent Mouliere, Safia El Messaoudi, Celine Gongora, Anne-Sophie Guedj, Bruno Robert, Maguy Del Rio, Franck Molina, Pierre-Jean Lamy, Evelyne Lopez-Crapez, Muriel Mathonnet and 3 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Translational oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03828799 (Safety, Tolerability and Efficacy of Regorafenib in Combination With FOLFIRINOX in Patients With RAS-mutated Metastatic Colorectal Cancer), which is not on this map. Cited by 82 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 2 pooled it
5.1field-weighted citation impact, top 4% 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.

NCT03828799 phase1 / phase2completednot on this mapstarted 2019, after this paper: background citation

Safety, Tolerability and Efficacy of Regorafenib in Combination With FOLFIRINOX in Patients With RAS-mutated Metastatic Colorectal Cancer: a Dose-escalation, Phase I/II Trial

TypeinterventionalSponsorInstitut du Cancer de Montpellier - Val d'AurelleRan2019 to 2024Enrolled13ConditionsMetastatic Colorectal CancerArmsFolfirinox + regorafenib
3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 155 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. Trial
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

22 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 7 institutions in 1 country.

Florent MouliereInstitut de Recherche en Cancérologie de Montpellier, Montpellier, France ; Institut National de la Santé et de la Recherche Médicale, U896, Montpellier, France ; Université Montpellier 1, Montpellier, France ; Institut régional du Cancer Montpellier, Montpellier, France ; Sysdiag UMR3145, Centre National de la Recherche Scientifique/Bio-Rad, Montpellier, France.
Safia El Messaoudi
Celine Gongora
Anne-Sophie Guedj
Bruno Robert
Maguy Del Rio
Franck Molina
Pierre-Jean Lamy
Evelyne Lopez-Crapez
Muriel Mathonnet
Marc Ychou
Denis Pezet
Alain R Thierry
Bio-Rad (France) · FRInstitut de Recherche en Cancérologie de Montpellier · FRUniversité de Montpellier · FRCentre Hospitalier Universitaire de Clermont-Ferrand · FRCentre Hospitalier Universitaire de Limoges · FRGefluc Languedoc Roussillon · FRInstitut Regional du Cancer de Montpellier

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We used a novel method based on allele-specific quantitative polymerase chain reaction (Intplex) for the analysis of circulating cell.free DNA (ccfDNA) to compare total ccfDNA and KRAS- or BRAF-mutated ccfDNA concentrations in blood samples from mice xenografted with the human SW620 colorectal cancer (CRC) cell line and from patients with CRC. Intplex enables single-copy detection of variant alleles down to a sensitivity of ≥0.005 mutant to wild-type ratio. The proportion of mutant allele corresponding to the percentage of tumor-derived ccfDNA was elevated in xenografted mice with KRAS homozygous mutation and varied highly from 0.13% to 68.7% in samples from mutation-positive CRC patients (n = 38). Mutant ccfDNA alleles were quantified in the plasma of every patient at stages II/III and IV with a mean of 8.4% (median, 8.4%) and 21.8% (median, 12.4%), respectively. Twelve of 38 (31.6%) and 5 of 38 (13.2%) samples showed a mutation load higher than 25%and 50%, respectively. This suggests that an important part of ccfDNA may originate from tumor cells. In addition, we observed that tumor-derived (mutant) ccfDNA was more fragmented than ccfDNA from normal tissues. This observation suggests that the form of tumor-derived and normal ccfDNA could differ. Our approach revealed that allelic dilution is much less pronounced than previously stated, considerably facilitating the noninvasive molecular analysis of tumors.

Identifiers

PMID23730412
PMCPMC3660801
OpenAlexW2073581762

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.