title: Molecular profiling of lung adenosquamous carcinoma: hybrid or genuine type?
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.
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Erik
authors.initials: E
authors.lastname: Vassella
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Langsch
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Matthias S
authors.initials: MS
authors.lastname: Dettmer
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schlup
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Maja
authors.initials: M
authors.lastname: Neuenschwander
authors.affiliation: Institute of Pathology, Locarno, Switzerland.
authors.forename: Milo
authors.initials: M
authors.lastname: Frattini
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.|Promed SA Laboratoire Medical, Fribourg, Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Gugger
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Schäfer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D018196:Carcinoma, Adenosquamous / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015723:Gene Library; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D015398:Signal Transduction; D044465:White People
chemical_list: D004273:DNA, Neoplasm; D066246:ErbB Receptors; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D016283:Proto-Oncogene Proteins p21(ras); C117307:KRAS protein, human; C534425:MIR205, human; C512478:EGFR protein, human
keywords: adenosquamous carcinoma; lung; microRNA; next-generation sequencing; therapy-relevant mutation