Oncotarget

Research Papers:

MET exon 14 mutations as targets in routine molecular analysis of primary sarcomatoid carcinoma of the lung

Raphaël Saffroy, Vincent Fallet, Nicolas Girard, Julien Mazieres, Denis Moro Sibilot, Sylvie Lantuejoul, Isabelle Rouquette, Françoise Thivolet-Bejui, Thibaut Vieira, Martine Antoine, Jacques Cadranel, Antoinette Lemoine and Marie Wislez _

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Oncotarget. 2017; 8:42428-42437. https://doi.org/10.18632/oncotarget.16403

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Abstract

Raphaël Saffroy1,2,*, Vincent Fallet3,4,*, Nicolas Girard5, Julien Mazieres6, Denis Moro Sibilot7, Sylvie Lantuejoul8, Isabelle Rouquette9, Françoise Thivolet-Bejui10, Thibaut Vieira3,4, Martine Antoine3,11, Jacques Cadranel3,4, Antoinette Lemoine1,2,* and Marie Wislez3,4,*

1Department of Biochemistry and Oncogenetics, AP-HP Hôpital Paul-Brousse, Hôpitaux Universitaire Paris Sud, Villejuif, France

2UMR-S 1193, Univ Paris-Sud, Université Paris-Saclay, Villejuif, France

3GRC n°04, Theranoscan, Sorbonne Universités, UPMC Univ Paris 06, Paris, France

4Pulmonary Medicine Unit, AP-HP, GH HUEP, Hôpital Tenon, Paris, France

5Respiratory Medicine, Thoracic Oncology Group, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France

6Pulmonary medicine Unit, Hôpital Larrey, Centre Hospitalier Universitaire, Toulouse, France

7Thoracic Oncology Unit, PTV, CHU Grenoble Alpes, Grenoble, France

8Department of Pathology, Hôpital A. Michallon, Centre Hospitalier Universitaire, Grenoble, France

9Centre Hospitalier Universitaire Rangueil, Service d’anatomie Pathologique, Toulouse, France

10Department of Pathology, Hôpital Louis Pradel, Lyon, France

11Department of Pathology, AP-HP, GH HUEP, Hôpital Tenon, Paris, France

*These authors have contributed equally to the work

Correspondence to:

Marie Wislez, email: [email protected]

Keywords: sarcomatoid carcinomas of the lung, non-small cell lung cancer, MET exon 14 skipping mutation

Received: August 08, 2016    Accepted: February 20, 2017    Published: March 21, 2017

ABSTRACT

MET exon 14 splicing mutations are new targetable oncogenic drivers reported in 3% of non-small cell lung cancer (NSCLC) cases and have been shown to be more common in pulmonary sarcomatoid carcinomas (PSCs). This study sought to screen mutations affecting MET exon 14 splice sites in a large SC cohort of Caucasian patients, with a large adenocarcinoma cohort as internal control.

We tested 81 patients with SC and 150 with adenocarcinoma for splice site DNA mutations leading to RNA splicing-based skipping of MET exon 14. To this end, we employed a mass spectrometry-based custom-designed PCR assay for routine analysis of whole MET exon 14 and flanking intronic regions using formalin-fixed paraffin-embedded (FFPE) tumor samples.

Our results revealed a 4.9% mutation rate for MET exon 14 mutations in Caucasian SC patients, which is, though highly variable, within the usual range reported in NSCLC. Discrepancies with previous results reported in SC could be accounted for the small number of cases, ethnicity, epithelial component, and percentage of other driver mutations, such as KRAS, in the patient populations studied. Based on our study findings, SC patients should be screened for MET exon 14 mutations in the same manner as adenocarcinoma patients.


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