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<datestamp>2017-12-21</datestamp>
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<publisher>HAL CCSD</publisher>
<title lang=en>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</title>
<creator>Dugay, Frédéric</creator>
<creator>Llamas-Gutierrez, Francisco</creator>
<creator>Gournay, Marjory</creator>
<creator>Médane, Sarah</creator>
<creator>Mazet, Francois</creator>
<creator>Chiforeanu, Dan Christian</creator>
<creator>Becker, Emmanuelle</creator>
<creator>Lamy, Régine</creator>
<creator>Léna, Hervé</creator>
<creator>Rioux-Leclercq, Nathalie</creator>
<creator>Belaud-Rotureau, Marc-Antoine</creator>
<creator>Cabillic, Florian</creator>
<contributor>Service de Cytogénétique et de Biologie Cellulaire ; Université de Rennes 1 (UR1) - Hôpital Pontchaillou - CHU Pontchaillou [Rennes]</contributor>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Service d'hématologie clinique ; Université de Rennes 1 (UR1) - Hôpital Pontchaillou</contributor>
<contributor>CH Bretagne Sud</contributor>
<contributor>Service de pneumologie ; Université de Rennes 1 (UR1) - CHU Pontchaillou [Rennes]</contributor>
<contributor>Nutrition, Métabolismes et Cancer (NuMeCan) ; Université de Rennes 1 (UR1) - Institut National de la Santé et de la Recherche Médicale (INSERM)</contributor>
<description>International audience</description>
<source>ISSN: 1949-2553</source>
<source>Oncotarget</source>
<publisher>Impact journals</publisher>
<identifier>hal-01578586</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578586</identifier>
<source>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578586</source>
<source>Oncotarget, Impact journals, 2017, 8 (32), pp.53336--53351. 〈10.18632/oncotarget.18408〉</source>
<identifier>DOI : 10.18632/oncotarget.18408</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.18408</relation>
<identifier>PUBMED : 28881815</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/28881815</relation>
<language>en</language>
<subject lang=en> ros1</subject>
<subject lang=en> ret</subject>
<subject lang=en> fusion genes</subject>
<subject lang=en> caucasian population</subject>
<subject lang=en>non-small cell lung cancer</subject>
<subject>[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>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.</description>
<date>2017</date>
</dc>
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