TRK Fusions Are Enriched in Cancers with Uncommon Histologies and the Absence of Canonical Driver Mutations.
Adolescent
Adult
Aged
Biomarkers, Tumor
/ genetics
Child
Child, Preschool
Female
Genomics
Humans
Infant
Infant, Newborn
Male
Membrane Glycoproteins
/ genetics
Microsatellite Instability
Middle Aged
Molecular Targeted Therapy
/ methods
Mutation
Neoplasms
/ drug therapy
Protein Kinase Inhibitors
/ therapeutic use
Proteins
/ antagonists & inhibitors
Receptor, trkA
/ genetics
Receptor, trkB
/ genetics
Receptor, trkC
/ genetics
Young Adult
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 04 2020
01 04 2020
Historique:
received:
27
09
2019
revised:
14
11
2019
accepted:
19
12
2019
pubmed:
25
12
2019
medline:
23
1
2021
entrez:
25
12
2019
Statut:
ppublish
Résumé
TRK inhibitors achieve marked tumor-agnostic efficacy in TRK fusion-positive cancers and consequently are now an established standard of care. Little is known, however, about the demographics, outcomes, response to alternative standard therapies, or genomic characteristics of TRK fusion-positive cancers. Utilizing a center-wide screening program involving more than 26,000 prospectively sequenced patients, genomic and clinical data from all cases with TRK fusions were extracted. An integrated analysis was performed of genomic, therapeutic, and phenomic outcomes. We identified 76 cases with confirmed TRK fusions (0.28% overall prevalence) involving 48 unique rearrangements and 17 cancer types. The presence of a TRK fusion was associated with depletion of concurrent oncogenic drivers ( TRK fusion-positive cancers can respond to alternative standards of care, although efficacy of immunotherapy in the absence of other predictive biomarkers (MSI-H) appears limited. TRK fusions are present in tumors with simple genomes lacking in concurrent drivers that may partially explain the tumor-agnostic efficacy of TRK inhibitors.
Identifiants
pubmed: 31871300
pii: 1078-0432.CCR-19-3165
doi: 10.1158/1078-0432.CCR-19-3165
pmc: PMC7124988
mid: NIHMS1547507
doi:
Substances chimiques
Biomarkers, Tumor
0
Membrane Glycoproteins
0
NTRK1 protein, human
0
NTRK3 protein, human
0
Protein Kinase Inhibitors
0
Proteins
0
TFG protein, human
0
Receptor, trkA
EC 2.7.10.1
Receptor, trkB
EC 2.7.10.1
Receptor, trkC
EC 2.7.10.1
tropomyosin-related kinase-B, human
EC 2.7.10.1
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
1624-1632Subventions
Organisme : NCI NIH HHS
ID : T32 CA160001
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA226864
Pays : United States
Organisme : NCI NIH HHS
ID : R25 CA020449
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009512
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009207
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR002385
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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