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

  • Vassella E Institute of Pathology, University of Bern, Bern, Switzerland.
  • Langsch S Institute of Pathology, University of Bern, Bern, Switzerland.
  • Dettmer MS Institute of Pathology, University of Bern, Bern, Switzerland.
  • Schlup C Institute of Pathology, University of Bern, Bern, Switzerland.
  • Neuenschwander M Institute of Pathology, University of Bern, Bern, Switzerland.
  • Frattini M Institute of Pathology, Locarno, Switzerland.
  • Gugger M Institute of Pathology, University of Bern, Bern, Switzerland.
  • Schäfer SC Institute of Pathology, University of Bern, Bern, Switzerland.
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  • 2015-06-13
Published in:
  • Oncotarget. - 2015
adenosquamous carcinoma
lung
microRNA
next-generation sequencing
therapy-relevant mutation
Aged
Aged, 80 and over
Base Sequence
Carcinoma, Adenosquamous
Carcinoma, Squamous Cell
DNA Mutational Analysis
DNA, Neoplasm
ErbB Receptors
European Continental Ancestry Group
Female
Gene Expression Profiling
Gene Library
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Lung Neoplasms
Male
MicroRNAs
Middle Aged
Molecular Sequence Data
Mutation
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins p21(ras)
Signal Transduction
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/285626
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