Evidence map›Paper›PMID 24983367›Full record

ArticleBritish journal of cancer2014

Validation and utilisation of high-coverage next-generation sequencing to deliver the pharmacological audit trail.

M Ong, S Carreira, J Goodall, J Mateo, I Figueiredo, D N Rodrigues, G Perkins, G Seed, T A Yap, G Attard and 1 more

Abstract read
In one paragraph

Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
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

16 citing papers in PubMed.

  1. Trial
  2. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.The New England journal of medicine · 2015
    Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Phase I Study of an AKT Inhibitor (MK-2206) Combined with Lapatinib in Adult Solid Tumors Followed by Dose Expansion in Advanced HER2+ Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016
    Article
  11. Article
  12. Article
  13. Article
  14. Serial Next-Generation Sequencing of Circulating Cell-Free DNA Evaluating Tumor Clone Response To Molecularly Targeted Drug Administration.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015
    Article
  15. Review
  16. Review
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.

M Ong1] Cancer Biomarkers Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK [2] Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK.
S Carreira1] Cancer Biomarkers Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK [2] Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK.
J Goodall1] Cancer Biomarkers Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK [2] Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK.
J Mateo1] Cancer Biomarkers Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK [2] Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK.
I FigueiredoCancer Biomarkers Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
D N RodriguesCancer Biomarkers Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
G PerkinsCancer Biomarkers Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
G SeedCancer Biomarkers Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
T A Yap1] Cancer Biomarkers Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK [2] Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK.
G Attard1] Cancer Biomarkers Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK [2] Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK.
J S de Bono1] Cancer Biomarkers Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK [2] Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK.

Funding

Cancer Research UK 13239Cancer Research UK A13239Department of HealthProstate Cancer UK PG12-49
6 · The paper itself

Abstract

backgroundPredictive biomarker development is a key challenge for novel cancer therapeutics. We explored the feasibility of next-generation sequencing (NGS) to validate exploratory genomic biomarkers that impact phase I trial selection.

methodsWe prospectively enrolled 158 patients with advanced solid tumours referred for phase I clinical trials at the Royal Marsden Hospital (October 2012 to March 2013). After fresh and/or archived tumour tissue were obtained, 93 patients remained candidates for phase I trials. Results from tumour sequencing on the Illumina MiSeq were cross-validated in 27 out of 93 patients on the Ion Torrent Personal Genome Machine (IT-PGM) blinded to results. MiSeq validation with Sequenom MassARRAY OncoCarta 1.0 (Sequenom Inc., San Diego, CA, USA) was performed in a separate cohort.

resultsWe found 97% concordance of mutation calls by MiSeq and IT-PGM at a variant allele frequency ⩾13% and ⩾500 × depth coverage, and 91% concordance between MiSeq and Sequenom. Common 'actionable' mutations involved deoxyribonucleic acid (DNA) repair (51%), RAS-RAF-MEK (35%), Wnt (26%), and PI3K-AKT-mTOR (24%) signalling. Out of 53, 29 (55%) patients participating in phase I trials were recommended based on identified actionable mutations.

conclusionsTargeted high-coverage NGS panels are a highly feasible single-centre technology well-suited to cross-platform validation, enrichment of trials with molecularly defined populations and hypothesis testing early in drug development.

Indexed as

AdultAgedBiomarkers, TumorFemaleGene FrequencyHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedMutationNeoplasmsProspective StudiesReproducibility of ResultsSequence Analysis, DNAYoung AdultBiomarkers, Tumor

Identifiers

PMID24983367
PMCPMC4150267

What OpenQuestion holds

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LicenceCC BY-NC-SA
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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.