Diagnostic classification of childhood cancer using multiscale transcriptomics.

Adult Humans Child Neoplasms / diagnosis Transcriptome / genetics Prospective Studies Gene Expression Profiling / methods Neural Networks, Computer

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
03 2023
Historique:
received: 21 03 2022
accepted: 13 01 2023
pubmed: 19 3 2023
medline: 25 3 2023
entrez: 18 3 2023
Statut: ppublish

Résumé

The causes of pediatric cancers' distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types.

Identifiants

DOI: 10.1038/s41591-023-02221-x PMID: 36932241 PMC: PMC10033451
pubmed: 36932241
doi: 10.1038/s41591-023-02221-x
pii: 10.1038/s41591-023-02221-x
pmc: PMC10033451
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

656-666

Subventions

Organisme : CIHR
ID : 162267
Pays : Canada

Informations de copyright

© 2023. The Author(s).

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Auteurs

Federico Comitani (F)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
ORCID: 0000-0003-3226-1179

Joshua O Nash (JO)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Laboratory of Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Sarah Cohen-Gogo (S)

Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
ORCID: 0000-0002-8852-1104

Astra I Chang (AI)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Timmy T Wen (TT)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Anant Maheshwari (A)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Bipasha Goyal (B)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Earvin S Tio (ES)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
ORCID: 0000-0002-0521-779X

Kevin Tabatabaei (K)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Chelsea Mayoh (C)

Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia.
ORCID: 0000-0002-6398-3046

Regis Zhao (R)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Ben Ho (B)

Laboratory of Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.

Ledia Brunga (L)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

John E G Lawrence (JEG)

Wellcome Sanger Institute, Hinxton, UK.

Petra Balogh (P)

Department of Cellular and Molecular Pathology, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, UK.

Adrienne M Flanagan (AM)

Department of Cellular and Molecular Pathology, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, UK.
Research Department of Pathology, University College London Cancer Institute, London, UK.
ORCID: 0000-0002-2832-1303

Sarah Teichmann (S)

Wellcome Sanger Institute, Hinxton, UK.
ORCID: 0000-0002-6294-6366

Annie Huang (A)

Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
Medical Biophysics, University of Toronto, Toronto, ON, Canada.

Vijay Ramaswamy (V)

Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Medical Biophysics, University of Toronto, Toronto, ON, Canada.
ORCID: 0000-0002-6557-895X

Johann Hitzler (J)

Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
ORCID: 0000-0003-1158-186X

Jonathan D Wasserman (JD)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
ORCID: 0000-0001-7088-8146

Rebecca A Gladdy (RA)

Department of Surgical Oncology, Princess Margaret Cancer Centre/Mount Sinai Hospital, Toronto, ON, Canada.
Department of Surgery, University of Toronto, Toronto, ON, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
ORCID: 0000-0003-4143-6620

Brendan C Dickson (BC)

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
ORCID: 0000-0003-2269-6216

Uri Tabori (U)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
ORCID: 0000-0002-5019-2683

Mark J Cowley (MJ)

Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia.
ORCID: 0000-0002-9519-5714

Sam Behjati (S)

Wellcome Sanger Institute, Hinxton, UK.
Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Department of Paediatrics, University of Cambridge, Cambridge, UK.
ORCID: 0000-0002-6600-7665

David Malkin (D)

Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Medical Biophysics, University of Toronto, Toronto, ON, Canada.
ORCID: 0000-0001-5752-9763

Anita Villani (A)

Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.

Meredith S Irwin (MS)

Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Medical Biophysics, University of Toronto, Toronto, ON, Canada.

Adam Shlien (A)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada. adam.shlien@sickkids.ca.
Laboratory of Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. adam.shlien@sickkids.ca.
ORCID: 0000-0002-0368-5370

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Diagnostic classification of childhood cancer...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Diagnostic classification of childhood cancer...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Diagnostic classification of childhood cancer...
questionsmedicales.fr › Tumeurs › Diagnostic classification of childhood cancer...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Diagnostic classification of childhood cancer...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Diagnostic classification of childhood cancer...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Diagnostic classification of childhood cancer...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Algorithmes › Intelligence artificielle › Réseaux neuronaux (ordinateur) › Diagnostic classification of childhood cancer...