Novel CAD-ALK gene rearrangement is drugable by entrectinib in colorectal cancer.

Content Provider	Europe PMC
Author	Amatu, Alessio Somaschini, Alessio Cerea, Giulio Bosotti, Roberta Valtorta, Emanuele Buonandi, Pasquale Marrapese, Giovanna Veronese, Silvio Luo, David Hornby, Zachary Multani, Pratik Murphy, Danielle Shoemaker, Robert Lauricella, Calogero Giannetta, Laura Maiolani, Martina Vanzulli, Angelo Ardini, Elena Galvani, Arturo Isacchi, Antonella Sartore-Bianchi, Andrea Siena, Salvatore
Copyright Year	2015
Abstract	Background:Activated anaplastic lymphoma kinase (ALK) gene fusions are recurrent events in a small fraction of colorectal cancers (CRCs), although these events have not yet been exploited as in other malignancies.Methods:We detected ALK protein expression by immunohistochemistry and gene rearrangements by fluorescence in situ hybridisation in the ALKA-372-001 phase I study of the pan-Trk, ROS1, and ALK inhibitor entrectinib. One out of 487 CRCs showed ALK positivity with a peculiar pattern that prompted further characterisation by targeted sequencing using anchored multiplex PCR.Results:A novel ALK fusion with the carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) gene (CAD-ALK fusion gene) was identified. It resulted from inversion within chromosome 2 and the fusion of exons 1–35 of CAD with exons 20–29 of ALK. After failure of previous standard therapies, treatment of this patient with the ALK inhibitor entrectinib resulted in a durable objective tumour response.Conclusions:We describe the novel CAD-ALK rearrangement as an oncogene and provide the first evidence of its drugability as a new molecular target in CRC.
ISSN	00070920
Journal	British Journal of Cancer
Volume Number	113
PubMed Central reference number	PMC4701996
Issue Number	12
PubMed reference number	26633560
e-ISSN	15321827
DOI	10.1038/bjc.2015.401
Language	English
Publisher	Nature Publishing Group
Publisher Date	2015-12-03
Access Restriction	Open
Rights License	This work is licensed under the Creative Commons Attribution-Non-Commercial-Share Alike 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ Copyright © 2015 Cancer Research UK
Subject Keyword	entrectinib gene fusions colorectal cancer CAD-ALK ALK
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology