Oncotarget

Research Papers:

Molecular profiling of lung adenosquamous carcinoma: hybrid or genuine type?

Erik Vassella _, Stephanie Langsch, Matthias S. Dettmer, Cornelia Schlup, Maja Neuenschwander, Milo Frattini, Mathias Gugger and Stephan C. Schäfer

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Oncotarget. 2015; 6:23905-23916. https://doi.org/10.18632/oncotarget.4163

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Abstract

Erik Vassella1, Stephanie Langsch1, Matthias S. Dettmer1, Cornelia Schlup1, Maja Neuenschwander1, Milo Frattini2, Mathias Gugger1,3, Stephan C. Schäfer1,4

1Institute of Pathology, University of Bern, Bern, Switzerland

2Institute of Pathology, Locarno, Switzerland

3Promed SA Laboratoire Medical, Fribourg, Switzerland

4Institute of Pathology, University Hospital of Cologne, Cologne, Germany

Correspondence to:

Erik Vassella, e-mail: erik.vassella@pathology.unibe.ch

Keywords: adenosquamous carcinoma, lung, next-generation sequencing, therapy-relevant mutation, microRNA

Received: March 17, 2015     Accepted: May 15, 2015     Published: June 03, 2015

ABSTRACT

Lung adenosquamous carcinoma is a particular subtype of non-small cell lung carcinoma that is defined by the coexistence of adenocarcinoma and squamous cell carcinoma components. The aim of this study was to assess the mutational profile in each component of 16 adenosquamous carcinoma samples from a Caucasian population by a combination of next generation sequencing using the cancer hotspot panel as well as the colon and lung cancer panel and FISH. Identified mutations were confirmed by Sanger sequencing of DNA from cancer cells of each component collected by Laser Capture microdissection. Mutations typical for adenocarcinoma as well as squamous cell carcinoma were identified. Driver mutations were predominantly in the trunk suggesting a monoclonal origin of adenosquamous carcinoma. Most remarkably, EGFR mutations and mutations in the PI3K signaling pathway, which accounted for 30% and 25% of tumors respectively, were more prevalent while KRAS mutations were less prevalent than expected for a Caucasian population. Surprisingly, expression of classifier miR-205 was intermediate between that of classical adenocarcinoma and squamous cell carcinoma suggesting that adenosquamous carcinoma is a transitional stage between these tumor types. The high prevalence of therapy-relevant targets opens new options of therapeutic intervention for adenosquamous carcinoma patients.


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