Standardized evidence-based approach for assessment of oncogenic and clinical significance of NTRK fusions.
actionable
biomarker
curation
oncogenicity
pathogenicity
reading-frame
Journal
Cancer genetics
ISSN: 2210-7762
Titre abrégé: Cancer Genet
Pays: United States
ID NLM: 101539150
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
18
10
2021
revised:
13
02
2022
accepted:
07
03
2022
pubmed:
3
4
2022
medline:
26
5
2022
entrez:
2
4
2022
Statut:
ppublish
Résumé
Gene fusions involving the neurotrophic receptor tyrosine kinase genes NTRK1, NTRK2, and NTRK3, are well established oncogenic drivers in a broad range of pediatric and adult tumors. These fusions are also important actionable markers, predicting often dramatic response to FDA approved kinase inhibitors. Accurate interpretation of the clinical significance of NTRK fusions is a high priority for diagnostic laboratories, but remains challenging and time consuming given the rapid pace of new data accumulation, the diversity of fusion partners and tumor types, and heterogeneous and incomplete information in variant databases and knowledgebases. The ClinGen NTRK Fusions Somatic Cancer Variant Curation Expert Panel (SC-VCEP) was formed to systematically address these challenges and create an expert-curated resource to support clinicians, researchers, patients and their families in making accurate interpretations and informed treatment decisions for NTRK fusion-driven tumors. We describe a system for NTRK fusion interpretation (including compilation of key elements and annotations) developed by the NTRK fusions SC-VCEP. We illustrate this stepwise process on examples of LMNA::NTRK1 and KANK1::NTRK2 fusions. Finally, we provide detailed analysis of current representation of NTRK fusions in public fusion databases and the CIViC knowledgebase, performed by the NTRK fusions SC-VCEP to determine existing gaps and prioritize future curation activities.
Identifiants
pubmed: 35366592
pii: S2210-7762(22)00024-2
doi: 10.1016/j.cancergen.2022.03.001
pmc: PMC9252326
mid: NIHMS1802977
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Biomarkers, Tumor
0
Cytoskeletal Proteins
0
KANK1 protein, human
0
Oncogene Proteins, Fusion
0
Receptor, trkA
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
50-59Subventions
Organisme : NHGRI NIH HHS
ID : U24 HG009649
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA237719
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG009650
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG006834
Pays : United States
Organisme : NHGRI NIH HHS
ID : R00 HG007940
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
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