CINECA IRIS Institutional Research Information System
IRIS è il sistema di gestione integrata dei dati della ricerca (persone, progetti, pubblicazioni, attività) adottato dall'Università degli Studi di Torino.
AperTO è l'archivio istituzionale Open Access destinato a raccogliere, rendere visibile e conservare la produzione scientifica dell'Università degli Studi di Torino.
EnglishThe development of molecularly targeted anticancer agents relies on large panels of tumour-specific preclinical models closely recapitulating the molecular heterogeneity observed in patients. Here we describe the mutational and gene expression analyses of 151 colorectal cancer (CRC) cell lines. We find that the whole spectrum of CRC molecular and transcriptional subtypes, previously defined in patients, is represented in this cell line compendium. Transcriptional outlier analysis identifies RAS/BRAF wild-type cells, resistant to EGFR blockade, functionally and pharmacologically addicted to kinase genes including ALK, FGFR2, NTRK1/2 and RET. The same genes are present as expression outliers in CRC patient samples. Genomic rearrangements (translocations) involving the ALK and NTRK1 genes are associated with the overexpression of the corresponding proteins in CRC specimens. The approach described here can be used to pinpoint CRCs with exquisite dependencies to individual kinases for which clinically approved drugs are already available.
| Titolo: | The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets | |
| Autori Riconosciuti: | ||
| Autori: | Medico, E; Russo, M; Picco, G; Cancelliere, C; Valtorta, E; Corti, G; Buscarino, M; Isella, C; Lamba, S; Martinoglio, B; Veronese, S; Siena, S; Sartore-Bianchi, A; Beccuti, M; Mottolese, M; Linnebacher, M; Cordero, F; Di Nicolantonio, F*; Bardelli, A*; (*co-last and *corresponding authors) | |
| Data di pubblicazione: | 2015 | |
| Abstract: | The development of molecularly targeted anticancer agents relies on large panels of tumour-specific preclinical models closely recapitulating the molecular heterogeneity observed in patients. Here we describe the mutational and gene expression analyses of 151 colorectal cancer (CRC) cell lines. We find that the whole spectrum of CRC molecular and transcriptional subtypes, previously defined in patients, is represented in this cell line compendium. Transcriptional outlier analysis identifies RAS/BRAF wild-type cells, resistant to EGFR blockade, functionally and pharmacologically addicted to kinase genes including ALK, FGFR2, NTRK1/2 and RET. The same genes are present as expression outliers in CRC patient samples. Genomic rearrangements (translocations) involving the ALK and NTRK1 genes are associated with the overexpression of the corresponding proteins in CRC specimens. The approach described here can be used to pinpoint CRCs with exquisite dependencies to individual kinases for which clinically approved drugs are already available. | |
| Volume: | 6 | |
| Fascicolo: | 7002 | |
| Pagina iniziale: | 1 | |
| Pagina finale: | 10 | |
| Digital Object Identifier (DOI): | 10.1038/ncomms8002 | |
| URL: | http://www.nature.com/ncomms/2015/150430/ncomms8002/full/ncomms8002.html http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE59857 | |
| Parole Chiave: | colorectal cancer; EGFR; cetuximab; Tyrosine kinase inhibition | |
| Rivista: | NATURE COMMUNICATIONS | |
| Appare nelle tipologie: | 03A-Articolo su Rivista |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| Medico_CRC_encyclopedia_NatComm_2015_Aperto.pdf | POSTPRINT (VERSIONE FINALE DELL’AUTORE) | Accesso aperto | Open Access Visualizza/Apri | |
| 2015_Medico_CRC_encyclopedia_NatComm_Article+SI.pdf | PDF EDITORIALE | Accesso riservato | Utenti riconosciuti Richiedi una copia |
Copyright © 2022