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Nat Commun. 2015 Apr 30;6:7002. doi: 10.1038/ncomms8002.

The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets.

Author information

1
1] Department of Oncology, University of Torino, SP 142, Km 3.95, 10060, Candiolo, Torino, Italy [2] Candiolo Cancer Institute-FPO, IRCCS, 10060, Candiolo (TO), Italy.
2
1] Department of Oncology, University of Torino, SP 142, Km 3.95, 10060, Candiolo, Torino, Italy [2] Candiolo Cancer Institute-FPO, IRCCS, 10060, Candiolo (TO), Italy [3] FIRC Institute of Molecular Oncology (IFOM), 20139 Milano, Italy.
3
Candiolo Cancer Institute-FPO, IRCCS, 10060, Candiolo (TO), Italy.
4
Department of Hematology and Oncology, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, 20162 Milan, Italy.
5
Department of Oncology, University of Torino, SP 142, Km 3.95, 10060, Candiolo, Torino, Italy.
6
Department of Computer Science, University of Torino, 10149 Torino, Italy.
7
S.C. Anatomia Patologica, Istituto Nazionale Tumori Regina Elena, 00144 Roma, Italy.
8
Division of Molecular Oncology and Immunotherapy, University of Rostock, D-18057 Rostock, Germany.

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.

PMID:
25926053
DOI:
10.1038/ncomms8002
[Indexed for MEDLINE]
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