Evidence map›Paper›PMID 31543384›Full record

ArticleEuropean journal of cancer (Oxford, England : 1990)2019

A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations.

Sally L George, Elisa Izquierdo, James Campbell, Eleni Koutroumanidou, Paula Proszek, Sabri Jamal, Deborah Hughes, Lina Yuan, Lynley V Marshall, Fernando Carceller and 27 more

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

Article in European journal of cancer (Oxford, England : 1990), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 3 pooled it
2.5field-weighted citation impact, top 10% 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

37 citing papers in PubMed, 3 syntheses or guidelines pooled it, 91 citations in OpenAlex.

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  13. Integration of Genomic Sequencing Drives Therapeutic Targeting of PDGFRA in T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
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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

37 authors at 6 institutions in 3 countries.

Sally L GeorgePaediatric Tumour Biology, Division of Clinical Studies, The Institute of Cancer Research, London, UK; Children and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK. Electronic address: sally.george@icr.ac.uk.
Elisa IzquierdoMolecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK; Glioma Team, Division of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
James CampbellBioinformatics Core Facility, The Institute of Cancer Research, London, UK.
Eleni KoutroumanidouMolecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK.
Paula ProszekMolecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK.
Sabri JamalMolecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK.
Deborah HughesMolecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK.
Lina YuanMolecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK.
Lynley V MarshallPaediatric Tumour Biology, Division of Clinical Studies, The Institute of Cancer Research, London, UK; Children and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK.
Fernando CarcellerPaediatric Tumour Biology, Division of Clinical Studies, The Institute of Cancer Research, London, UK; Children and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK.
Julia C ChisholmPaediatric Tumour Biology, Division of Clinical Studies, The Institute of Cancer Research, London, UK; Children and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK.
Sucheta VaidyaPaediatric Tumour Biology, Division of Clinical Studies, The Institute of Cancer Research, London, UK; Children and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK.
Henry MandevilleChildren and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK.
Paola AngeliniChildren and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK.
Ajla WastiChildren and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK.
Tomas BexeliusChildren and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK.
Khin ThwayPathology Department, Royal Marsden NHS Foundation Trust, London, UK.
Susanne A GatzChildren and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK; Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK; Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Matthew ClarkeGlioma Team, Division of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
Bissan Al-LazikaniBioinformatics Core Facility, The Institute of Cancer Research, London, UK.
Giuseppe BaroneDepartment of Haematology and Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
John AndersonDepartment of Haematology and Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; Developmental Biology and Cancer Programme, UCL GOS Institute of Child Health, London, UK.
Deborah A TweddleNorthern Institute for Cancer Research, Newcastle University, Newcastle, UK.
David GonzalezMolecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK; Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast, UK.
Brian A WalkerMolecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK; Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Jack BartonDevelopmental Biology and Cancer Programme, UCL GOS Institute of Child Health, London, UK.
Sarita DepaniDepartment of Haematology and Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Jessica EzeDepartment of Haematology and Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; Department of Histology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Saira W AhmedDepartment of Haematology and Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; Department of Histology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Lucas MorenoChildren and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK; HNJ-CNIO Clinical Research Unit, Hospital Universitario Nino Jesus, Madrid, Spain; Paediatric Oncology & Haematology, Vall d'Hebron University Hospital, Barcelona, Spain.
Andrew PearsonChildren and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK.
Janet ShipleySarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
Chris JonesGlioma Team, Division of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
Darren HargraveCancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK; Department of Haematology and Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Thomas S JacquesDepartment of Haematology and Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; Department of Histology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Michael HubankMolecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK.
Louis CheslerPaediatric Tumour Biology, Division of Clinical Studies, The Institute of Cancer Research, London, UK; Children and Young People's Unit, Royal Marsden NHS Foundation Trust, London, UK.
Royal Marsden NHS Foundation Trust · GBInstitute of Cancer Research · GBGreat Ormond Street Hospital for Children NHS Foundation Trust · GBNewcastle University · GBQueen's University Belfast · GBUniversity College London · GB

Funding

Cancer Research UK 22897Cancer Research UK 23187Cancer Research UK 24566Cancer Research UK 28028
6 · The paper itself

Abstract

backgroundFor children with cancer, the clinical integration of precision medicine to enable predictive biomarker-based therapeutic stratification is urgently needed.

methodsWe have developed a hybrid-capture next-generation sequencing (NGS) panel, specifically designed to detect genetic alterations in paediatric solid tumours, which gives reliable results from as little as 50 ng of DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. In this study, we offered an NGS panel, with clinical reporting via a molecular tumour board for children with solid tumours. Furthermore, for a cohort of 12 patients, we used a circulating tumour DNA (ctDNA)-specific panel to sequence ctDNA from matched plasma samples and compared plasma and tumour findings.

resultsA total of 255 samples were submitted from 223 patients for the NGS panel. Using FFPE tissue, 82% of all submitted samples passed quality control for clinical reporting. At least one genetic alteration was detected in 70% of sequenced samples. The overall detection rate of clinically actionable alterations, defined by modified OncoKB criteria, for all sequenced samples was 51%. A total of 8 patients were sequenced at different stages of treatment. In 6 of these, there were differences in the genetic alterations detected between time points. Sequencing of matched ctDNA in a cohort of extracranial paediatric solid tumours also identified a high detection rate of somatic alterations in plasma.

conclusionWe demonstrate that tailored clinical molecular profiling of both tumour DNA and plasma-derived ctDNA is feasible for children with solid tumours. Furthermore, we show that a targeted NGS panel-based approach can identify actionable genetic alterations in a high proportion of patients.

Indexed as

TranscriptomeAdolescentBiomarkers, TumorBiopsyChildChild, PreschoolCirculating Tumor DNADNA, NeoplasmFeasibility StudiesFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHigh-Throughput Nucleotide SequencingHumansInfantMaleBiomarkers, TumorCirculating Tumor DNADNA, NeoplasmCirculating tumour DNAClinical targeted sequencingPaediatric oncologyPersonalised medicine

Identifiers

PMID31543384
PMCPMC6839402
OpenAlexW2974820548

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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.