Extensive analysis of 59 sarcoma-related fusion genes identified pazopanib as a potential inhibitor to COL1A1-PDGFB fusion gene.
dermatofibrosarcoma protuberans
drug sensitivity
fusion gene
pazopanib
sarcoma
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
revised:
02
07
2023
received:
08
03
2023
accepted:
05
07
2023
pubmed:
18
8
2023
medline:
18
8
2023
entrez:
18
8
2023
Statut:
ppublish
Résumé
Sarcomas are malignant mesenchymal tumors that are extremely rare and divergent. Fusion genes are involved in approximately 30% of sarcomas as driver oncogenes; however, their detailed functions are not fully understood. In this study, we determined the functional significance of 59 sarcoma-related fusion genes. The transforming potential and drug sensitivities of these fusion genes were evaluated using a focus formation assay (FFA) and the mixed-all-nominated-in-one (MANO) method, respectively. The transcriptome was also examined using RNA sequencing of 3T3 cells transduced with each fusion gene. Approximately half (28/59, 47%) of the fusion genes exhibited transformation in the FFA assay, which was classified into five types based on the resulting phenotype. The sensitivity to 12 drugs including multityrosine kinase inhibitors was assessed using the MANO method and pazopanib was found to be more effective against cells expressing the COL1A1-PDGFB fusion gene compared with the others. The downstream MAPK/AKT pathway was suppressed at the protein level following pazopanib treatment. The fusion genes were classified into four subgroups by cluster analysis of the gene expression data and gene set enrichment analysis. In summary, the oncogenicity and drug sensitivity of 59 fusion genes were simultaneously evaluated using a high-throughput strategy. Pazopanib was selected as a candidate drug for sarcomas harboring the COL1A1-PDGFB fusion gene. This assessment could be useful as a screening platform and provides a database to evaluate customized therapy for fusion gene-associated sarcomas.
Identifiants
pubmed: 37592448
doi: 10.1111/cas.15915
pmc: PMC10551592
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4089-4100Subventions
Organisme : Fukuoka Public Health Promotion Organization Cancer Research Fund
Organisme : Japan Agency for Medical Research and Development
ID : JP20ck0106536
Organisme : Japan Society for the Promotion of Science
ID : JP21H02795
Informations de copyright
© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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