Identification and characterization of a novel SCYL3-NTRK1 rearrangement in a colorectal cancer patient

Massimo Milione, Elena Ardini, Jason Christiansen, Emanuele Valtorta, Silvio Veronese, Roberta Bosotti, Alessio Pellegrinelli, Adele Testi, Filippo Pietrantonio, Giovanni Fucà, Ge Wei, Danielle Murphy, Salvatore Siena, Antonella Isacchi, Filippo De Braud

Research output: Contribution to journalArticle

Abstract

In colorectal cancer patients, chromosomal rearrangements involving NTRK1 gene (encoding the TRKA protein) are shown in a small subset of patients and are associated with the constitutive activation of the kinase domain of TRKA. In turn, activated TRKA-fusion proteins are associated with proliferation and survival in colorectal cancer tumors. Here we report the identification and functional characterization of a new SCYL3-NTRK1 fusion gene in a 61-year-old colorectal cancer patient. To our knowledge, this fusion protein has never been previously documented in oncological patients. We show that this novel fusion is oncogenic and sensitive to TRKA inhibitors. As suggested by other pieces of evidence, entrectinib - an orally available pan- TRK, ROS1 and ALK inhibitor - may have particular efficacy in patients with NTRK rearrangements. Therefore, screening for rearrangements involving NTRK genes may help identifying a subset of patients able to derive benefit from treatment with entrectinib or other targeted inhibitors.

Original languageEnglish
Pages (from-to)55353-55360
Number of pages8
JournalOncotarget
Volume8
Issue number33
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Colorectal Neoplasms
Proteins
Gene Fusion
Genes
Phosphotransferases
Survival
entrectinib
Therapeutics

Keywords

  • CRC
  • Entrectinib
  • NTRK1
  • Rearrangement
  • TRKA

ASJC Scopus subject areas

  • Oncology

Cite this

Identification and characterization of a novel SCYL3-NTRK1 rearrangement in a colorectal cancer patient. / Milione, Massimo; Ardini, Elena; Christiansen, Jason; Valtorta, Emanuele; Veronese, Silvio; Bosotti, Roberta; Pellegrinelli, Alessio; Testi, Adele; Pietrantonio, Filippo; Fucà, Giovanni; Wei, Ge; Murphy, Danielle; Siena, Salvatore; Isacchi, Antonella; De Braud, Filippo.

In: Oncotarget, Vol. 8, No. 33, 01.01.2017, p. 55353-55360.

Research output: Contribution to journalArticle

Milione, M, Ardini, E, Christiansen, J, Valtorta, E, Veronese, S, Bosotti, R, Pellegrinelli, A, Testi, A, Pietrantonio, F, Fucà, G, Wei, G, Murphy, D, Siena, S, Isacchi, A & De Braud, F 2017, 'Identification and characterization of a novel SCYL3-NTRK1 rearrangement in a colorectal cancer patient', Oncotarget, vol. 8, no. 33, pp. 55353-55360. https://doi.org/10.18632/oncotarget.19512
Milione, Massimo ; Ardini, Elena ; Christiansen, Jason ; Valtorta, Emanuele ; Veronese, Silvio ; Bosotti, Roberta ; Pellegrinelli, Alessio ; Testi, Adele ; Pietrantonio, Filippo ; Fucà, Giovanni ; Wei, Ge ; Murphy, Danielle ; Siena, Salvatore ; Isacchi, Antonella ; De Braud, Filippo. / Identification and characterization of a novel SCYL3-NTRK1 rearrangement in a colorectal cancer patient. In: Oncotarget. 2017 ; Vol. 8, No. 33. pp. 55353-55360.
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