Integrated proteogenomic characterization of medullary thyroid carcinoma.
Journal
Cell discovery
ISSN: 2056-5968
Titre abrégé: Cell Discov
Pays: England
ID NLM: 101661034
Informations de publication
Date de publication:
08 Nov 2022
08 Nov 2022
Historique:
received:
23
04
2022
accepted:
30
09
2022
entrez:
7
11
2022
pubmed:
8
11
2022
medline:
8
11
2022
Statut:
epublish
Résumé
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy derived from parafollicular cells (C cells) of the thyroid. Here we presented a comprehensive multi-omics landscape of 102 MTCs through whole-exome sequencing, RNA sequencing, DNA methylation array, proteomic and phosphoproteomic profiling. Integrated analyses identified BRAF and NF1 as novel driver genes in addition to the well-characterized RET and RAS proto-oncogenes. Proteome-based stratification of MTCs revealed three molecularly heterogeneous subtypes named as: (1) Metabolic, (2) Basal and (3) Mesenchymal, which are distinct in genetic drivers, epigenetic modification profiles, clinicopathologic factors and clinical outcomes. Furthermore, we explored putative therapeutic targets of each proteomic subtype, and found that two tenascin family members TNC/TNXB might serve as potential prognostic biomarkers for MTC. Collectively, our study expands the knowledge of MTC biology and therapeutic vulnerabilities, which may serve as an important resource for future investigation on this malignancy.
Identifiants
pubmed: 36344509
doi: 10.1038/s41421-022-00479-y
pii: 10.1038/s41421-022-00479-y
pmc: PMC9640541
doi:
Types de publication
Journal Article
Langues
eng
Pagination
120Subventions
Organisme : Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality)
ID : 19ZR1410900
Organisme : Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality)
ID : 22ZR1412800
Organisme : Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality)
ID : 20YF1408200
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82002830
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82072951
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81772854
Informations de copyright
© 2022. The Author(s).
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