Oncotarget

Research Papers:

Clinicopathological characteristics of ROS1- and RET-rearranged NSCLC in caucasian patients: Data from a cohort of 713 non-squamous NSCLC lacking KRAS/EGFR/HER2/BRAF/PIK3CA/ALK alterations

Frédéric Dugay, Francisco Llamas-Gutierrez, Marjory Gournay, Sarah Medane, François Mazet, Dan Christian Chiforeanu, Emmanuelle Becker, Régine Lamy, Hervé Léna, Nathalie Rioux-Leclercq, Marc-Antoine Belaud-Rotureau and Florian Cabillic _

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Oncotarget. 2017; 8:53336-53351. https://doi.org/10.18632/oncotarget.18408

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Abstract

Frédéric Dugay1,2, Francisco Llamas-Gutierrez3, Marjory Gournay1, Sarah Medane1, François Mazet1, Dan Christian Chiforeanu3, Emmanuelle Becker2, Régine Lamy4, Hervé Léna5, Nathalie Rioux-Leclercq2,3, Marc-Antoine Belaud-Rotureau1,2 and Florian Cabillic1,6

1Department of Cytogenetics and Cell Biology, CHU de Rennes, Rennes, France

2IRSET UMR INSERM 1085, Faculté de Médecine, Université de Rennes 1, Rennes, France

3Department of Pathology, CHU de Rennes, Rennes, France

4Department of Pneumology, CHU de Lorient, Lorient, France

5Department of Pneumology, CHU de Rennes, Rennes, France

6INSERM, INRA, Université de Rennes 1, Université Bretagne Loire, Nutrition Metabolisms and Cancer, Rennes, France

Correspondence to:

Florian Cabillic, email: florian.cabillic@chu-rennes.fr

Keywords: non-small cell lung cancer, ROS1, RET, fusion genes, caucasian population

Received: December 12, 2016     Accepted: May 13, 2017     Published: June 08, 2017

ABSTRACT

Targeted therapies have substantially changed the management of non-small cell lung cancer (NSCLC) patients with driver oncogenes. Given the high frequency, EGFR and ALK aberrations were the first to be detected and paved the way for tyrosine kinase inhibitor (TKI) treatments. Other kinases such as ROS1 and more recently RET have emerged as promising targets, and ROS1 and RET TKIs are already available for precision medicine.

We screened a large cohort of 713 Caucasian non-squamous NSCLC patients lacking EGFR/KRAS/BRAF/HER2/PI3KCA/ALK aberrations for ROS1 and RET rearrangements using fluorescence in situ hybridization to determine the frequency and clinicopathological characteristics of ROS1- and RET-positive patients.

Frequencies of ROS1 and RET rearrangements were 2.1% and 2.52%, respectively. Contrary to common belief, both ROS1 and RET rearrangements were detected in patients with a history of smoking, and the RET-positive patients were not younger than the negative patients. Moreover, RET but not ROS1 rearrangement was associated with the female gender. Nearly half of the ROS1-rearranged patients were successfully treated with ROS1 TKIs. In contrast, only 5/18 RET-positive patients received off-label RET TKIs. Two patients had stable disease, and three experienced disease progression. In addition to the 18 RET-positive cases, 10 showed isolated 5’ signals. The clinical relevance is unknown but if the frequency is confirmed by other groups, the question whether these patients are eligible to TKIs will arise. More potent RET TKIs are under development and may improve the response rate in RET-positive patients. Therefore, we recommend the routine implementation of RET testing in non-squamous NSCLC patients, including those with a history of smoking.


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