Evidence map›Paper›PMID 26545243›Full record

ArticlePloS one2015

Evaluation of High-Throughput Genomic Assays for the Fc Gamma Receptor Locus.

Chantal E Hargreaves, Chisako Iriyama, Matthew J J Rose-Zerilli, Sietse Q Nagelkerke, Khiyam Hussain, Rosalind Ganderton, Charlotte Lee, Lee R Machado, Edward J Hollox, Helen Parker and 11 more

Erratum issuedAbstract readEvaluation StudyValidation Study
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Trial
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Chantal E HargreavesCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
Chisako IriyamaCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
Matthew J J Rose-ZerilliCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
Sietse Q NagelkerkeDepartment of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX, Amsterdam, The Netherlands.
Khiyam HussainCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
Rosalind GandertonMolecular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, United Kingdom.
Charlotte LeeMolecular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, United Kingdom.
Lee R MachadoDepartment of Genetics, University of Leicester, Leicester, LE1 7RH, United Kingdom.
Edward J HolloxDepartment of Genetics, University of Leicester, Leicester, LE1 7RH, United Kingdom.
Helen ParkerCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
Kate V LathamCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
Taco W KuijpersDepartment of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX, Amsterdam, The Netherlands.
Kathleen N PotterCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
Sarah E CouplandDepartment of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3GA, United Kingdom.
Andrew DaviesCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
Michael StackpoleDepartment of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3GA, United Kingdom.
Melanie OatesDepartment of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3GA, United Kingdom.
Andrew R PettittDepartment of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3GA, United Kingdom.
Martin J GlennieCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
Mark S CraggCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
Jonathan C StreffordCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.

Funding

Cancer Research UK 10015Cancer Research UK C328/A2737Cancer Research UK C328/A2738National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/C011204/1Wellcome TrustWellcome Trust 087663
6 · The paper itself

Abstract

Cancer immunotherapy has been revolutionised by the use monoclonal antibodies (mAb) that function through their interaction with Fc gamma receptors (FcγRs). The low-affinity FcγR genes are highly homologous, map to a complex locus at 1p23 and harbour single nucleotide polymorphisms (SNPs) and copy number variation (CNV) that can impact on receptor function and response to therapeutic mAbs. This complexity can hinder accurate characterisation of the locus. We therefore evaluated and optimised a suite of assays for the genomic analysis of the FcγR locus amenable to peripheral blood mononuclear cells and formalin-fixed paraffin-embedded (FFPE) material that can be employed in a high-throughput manner. Assessment of TaqMan genotyping for FCGR2A-131H/R, FCGR3A-158F/V and FCGR2B-232I/T SNPs demonstrated the need for additional methods to discriminate genotypes for the FCGR3A-158F/V and FCGR2B-232I/T SNPs due to sequence homology and CNV in the region. A multiplex ligation-dependent probe amplification assay provided high quality SNP and CNV data in PBMC cases, but there was greater data variability in FFPE material in a manner that was predicted by the BIOMED-2 multiplex PCR protocol. In conclusion, we have evaluated a suite of assays for the genomic analysis of the FcγR locus that are scalable for application in large clinical trials of mAb therapy. These assays will ultimately help establish the importance of FcγR genetics in predicting response to antibody therapeutics.

Indexed as

Antibodies, MonoclonalDNADNA Copy Number VariationsHigh-Throughput Nucleotide SequencingHumansLeukocytes, MononuclearMultiplex Polymerase Chain ReactionPolymorphism, Single NucleotideReceptors, IgGSequence Analysis, DNAAntibodies, MonoclonalDNAFCGR2A protein, humanFCGR2B protein, humanFCGR3A protein, humanReceptors, IgG

Identifiers

PMID26545243
PMCPMC4636148

What OpenQuestion holds

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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.