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.

Identification and characterization of a novel SCYL3-NTRK1 rearrangement in a colorectal cancer patient / M. Milione, E. Ardini, J. Christiansen, E. Valtorta, S. Veronese, R. Bosotti, A. Pellegrinelli, A. Testi, F. Pietrantonio, G. Fucà, G. Wei, D. Murphy, S. Siena, A. Isacchi, F. De Braud. - In: ONCOTARGET. - ISSN 1949-2553. - 8:33(2017), pp. 55353-55360. [10.18632/oncotarget.19512]

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

E. Valtorta;A. Pellegrinelli;F. Pietrantonio;G. Fucà;S. Siena;F. De Braud
2017

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.
CRC; Entrectinib; NTRK1; Rearrangement; TRKA
Settore MED/06 - Oncologia Medica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/552102
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