Genetic profiling of thymic carcinoma using targeted next-generation sequencing

Lung Cancer. 2014 Nov;86(2):174-9. doi: 10.1016/j.lungcan.2014.08.020. Epub 2014 Sep 10.

Abstract

Objectives: Thymic carcinoma is a rare mediastinal neoplasm and little is known about its tumorigenesis. There is no effective treatment except for complete resection, and the prognosis of advanced cases is poor. To identify the mutations associated with tumorigenesis, we analyzed genetic profile of thymic carcinoma using targeted next-generation sequencing.

Materials and methods: We sequenced about 409 cancer-related genes in 12 thymic squamous cell carcinoma tissues including 10 tumor/normal tissue pairs using Ion AmpliSeq Cancer Panel and Ion PGM Sequencer. We filtered the mutations with Ingenuity Variant Analysis, SIFT, PolyPhen-2, and PROVEAN.

Results and conclusion: Twenty-five candidate mutations in 24 genes were identified, including five tyrosine kinase genes (KIT, DDR2, PDGFRA, ROS1, IGF1R). There was no recurrent mutation among the samples studied. The KIT exon 11 deletion mutation in 1 patient was an activating mutation and may be an oncogenic driver mutation. Genetic profiling of thymic carcinoma using targeted next-generation sequencing was performed. The mutation status of thymic squamous cell carcinoma is highly heterogeneous.

Keywords: Genetic profiling; Heterogeneous; Squamous cell carcinoma; Targeted next-generation sequencing; Thymic carcinoma; Tyrosine kinase gene mutation.

MeSH terms

  • Aged
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Carcinoma / surgery
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Computational Biology
  • DNA Mutational Analysis
  • Female
  • Gene Expression Profiling*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Thymus Neoplasms / genetics*
  • Thymus Neoplasms / pathology
  • Thymus Neoplasms / surgery