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

Author

Listed:
  • Enzo Medico

    (University of Torino
    Candiolo Cancer Institute—FPO, IRCCS)

  • Mariangela Russo

    (University of Torino
    Candiolo Cancer Institute—FPO, IRCCS
    FIRC Institute of Molecular Oncology (IFOM))

  • Gabriele Picco

    (University of Torino
    Candiolo Cancer Institute—FPO, IRCCS)

  • Carlotta Cancelliere

    (Candiolo Cancer Institute—FPO, IRCCS)

  • Emanuele Valtorta

    (Niguarda Cancer Center, Ospedale Niguarda Ca’ Granda)

  • Giorgio Corti

    (Candiolo Cancer Institute—FPO, IRCCS)

  • Michela Buscarino

    (Candiolo Cancer Institute—FPO, IRCCS)

  • Claudio Isella

    (University of Torino)

  • Simona Lamba

    (University of Torino
    Candiolo Cancer Institute—FPO, IRCCS)

  • Barbara Martinoglio

    (Candiolo Cancer Institute—FPO, IRCCS)

  • Silvio Veronese

    (Niguarda Cancer Center, Ospedale Niguarda Ca’ Granda)

  • Salvatore Siena

    (Niguarda Cancer Center, Ospedale Niguarda Ca’ Granda)

  • Andrea Sartore-Bianchi

    (Niguarda Cancer Center, Ospedale Niguarda Ca’ Granda)

  • Marco Beccuti

    (University of Torino)

  • Marcella Mottolese

    (S.C. Anatomia Patologica, Istituto Nazionale Tumori Regina Elena)

  • Michael Linnebacher

    (University of Rostock)

  • Francesca Cordero

    (University of Torino)

  • Federica Di Nicolantonio

    (University of Torino
    Candiolo Cancer Institute—FPO, IRCCS)

  • Alberto Bardelli

    (University of Torino
    Candiolo Cancer Institute—FPO, IRCCS)

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.

Suggested Citation

  • Enzo Medico & Mariangela Russo & Gabriele Picco & Carlotta Cancelliere & Emanuele Valtorta & Giorgio Corti & Michela Buscarino & Claudio Isella & Simona Lamba & Barbara Martinoglio & Silvio Veronese &, 2015. "The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8002
    DOI: 10.1038/ncomms8002
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    Cited by:

    1. Simonetta M. Leto & Elena Grassi & Marco Avolio & Valentina Vurchio & Francesca Cottino & Martina Ferri & Eugenia R. Zanella & Sofia Borgato & Giorgio Corti & Laura Blasio & Desiana Somale & Marianela, 2024. "XENTURION is a population-level multidimensional resource of xenografts and tumoroids from metastatic colorectal cancer patients," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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