Oncotarget

Research Papers:

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 and Filippo De Braud

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Oncotarget. 2017; 8:55353-55360. https://doi.org/10.18632/oncotarget.19512

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Abstract

Massimo Milione1, Elena Ardini2, Jason Christiansen3, Emanuele Valtorta4, Silvio Veronese4, Roberta Bosotti2, Alessio Pellegrinelli1, Adele Testi1, Filippo Pietrantonio5, Giovanni Fucà6, Ge Wei3, Danielle Murphy3, Salvatore Siena4,5, Antonella Isacchi2 and Filippo De Braud5,6

11st Division of Pathology, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

2Nerviano Medical Sciences S.r.l., Milan, Italy

3Ignyta, Inc., San Diego, CA, United States of America

4Division of Pathology, Department of Laboratory Medicine, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy

5Dipartimento di Oncologia e Emato-Oncologia, Università degli Studi di Milano, Milan, Italy

6Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Correspondence to:

Massimo Milione, email: [email protected]

Keywords: NTRK1, TRKA, entrectinib, CRC, rearrangement

Received: April 12, 2017     Accepted: July 12, 2017     Published: July 24, 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.


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