Integrating molecular profiles into clinical frameworks through the Molecular Oncology Almanac to prospectively guide precision oncology.

Genomics / methods Humans Neoplasms / diagnosis Precision Medicine Prospective Studies Retrospective Studies

Journal

Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119

Informations de publication

Date de publication:
10 2021
Historique:
received: 24 09 2020
accepted: 14 07 2021
entrez: 5 2 2022
pubmed: 6 2 2022
medline: 6 4 2022
Statut: ppublish

Résumé

Tumor molecular profiling of single gene-variant ('first-order') genomic alterations informs potential therapeutic approaches. Interactions between such first-order events and global molecular features (for example, mutational signatures) are increasingly associated with clinical outcomes, but these 'second-order' alterations are not yet accounted for in clinical interpretation algorithms and knowledge bases. We introduce the Molecular Oncology Almanac (MOAlmanac), a paired clinical interpretation algorithm and knowledge base to enable integrative interpretation of multimodal genomic data for point-of-care decision making and translational-hypothesis generation. We benchmarked MOAlmanac to a first-order interpretation method across multiple retrospective cohorts and observed an increased number of clinical hypotheses from evaluation of molecular features and profile-to-cell line matchmaking. When applied to a prospective precision oncology trial cohort, MOAlmanac nominated a median of two therapies per patient and identified therapeutic strategies administered in 47% of patients. Overall, we present an open-source computational method for integrative clinical interpretation of individualized molecular profiles.

Identifiants

DOI: 10.1038/s43018-021-00243-3 PMID: 35121878 PMC: PMC9082009
pubmed: 35121878
doi: 10.1038/s43018-021-00243-3
pii: 10.1038/s43018-021-00243-3
pmc: PMC9082009
mid: NIHMS1794969
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1102-1112

Subventions

Organisme : NCI NIH HHS
ID : U01 CA233100
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227388
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA242861
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA222574
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021. The Author(s).

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Auteurs

Brendan Reardon (B)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Nathanael D Moore (ND)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Indiana University School of Medicine, Indianapolis, IN, USA.
Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.

Nicholas S Moore (NS)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Harvard Medical School, Harvard University, Boston, MA, USA.

Eric Kofman (E)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.

Saud H AlDubayan (SH)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA.
College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

Alexander T M Cheung (ATM)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Grossman School of Medicine, New York University, New York, NY, USA.

Jake Conway (J)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Division of Medical Sciences, Harvard University, Boston, MA, USA.

Haitham Elmarakeby (H)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of System and Computer Engineering, Al-Azhar University, Cairo, Egypt.
ORCID: 0000-0002-4315-4347

Alma Imamovic (A)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Sophia C Kamran (SC)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-9283-6515

Tanya Keenan (T)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Daniel Keliher (D)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Mathematics, Tufts University, Medford, MA, USA.

David J Konieczkowski (DJ)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Radiation Oncology, Dana-Farber Cancer Institute & Brigham and Women's Hospital, Boston, MA, USA.
Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, MA, USA.
Department of Radiation Oncology, the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, USA.

David Liu (D)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Kent W Mouw (KW)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Harvard Medical School, Harvard University, Boston, MA, USA.
Department of Radiation Oncology, Dana-Farber Cancer Institute & Brigham and Women's Hospital, Boston, MA, USA.

Jihye Park (J)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Natalie I Vokes (NI)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Thoracic/Head and Neck Oncology, MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-3766-5335

Felix Dietlein (F)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Eliezer M Van Allen (EM)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. eliezerm_vanallen@dfci.harvard.edu.
Broad Institute of MIT and Harvard, Cambridge, MA, USA. eliezerm_vanallen@dfci.harvard.edu.
ORCID: 0000-0002-0201-4444

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questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Integrating molecular profiles into clinical...
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questionsmedicales.fr › Tumeurs › Integrating molecular profiles into clinical...
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questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › Integrating molecular profiles into clinical...