Mutation Profile of Thymic Carcinoma and Thymic Neuroendocrine Tumor by Targeted Next-generation Sequencing

Clin Lung Cancer. 2021 Mar;22(2):92-99.e4. doi: 10.1016/j.cllc.2020.11.010. Epub 2020 Dec 2.


Background: Thymic carcinoma is a rare mediastinal neoplasm, and little is known about its genetic variability, which has hampered the development of targeted therapies.

Patients and methods: We tested a next-generation sequencing panel containing 50 common cancer-related genes in 48 cases of thymic carcinoma and 6 cases of thymic neuroendocrine tumor.

Results: We detected 42 variant calls in 21 of 54 cases. There was no significant difference in mutation frequency between thymic carcinoma and thymic neuroendocrine tumors. Among these, TP53 was the most frequently mutated gene (18.5%), followed by KIT (7.4%) and PDGFRA (5.6%). According to the gene pathways and groups, the p53 pathway, including TP53 and ATM, was most frequently affected (20.4%), followed by the receptor tyrosine kinase (RTK)/RAS pathway (18.5%) and PI3K pathway (5.6%). According to the OncoKB, an expert-guided precision oncology knowledge base, 7 genes among 10 cases (18.5%) were annotated with level 1 evidence, suggesting potentially therapeutic targets. Prognostic analyses, conducted in thymic squamous cell carcinomas, revealed that tumor cases harboring gene mutations in RTKs, including KIT (7.4%), PDGFRA (5.6%) and EGFR (3.7%), were significantly associated with a worse overall survival time (P = .0481). Among clinicopathologic factors, the advanced Masaoka stage was marginally associated with a worse overall survival (P = .0757). In the subsequent multivariate analysis, neither of the factors achieved statistical significance.

Conclusions: In this preliminary next-generation sequencing study, we unexpectedly found evidence suggesting that several gene mutations might be therapeutic targets. The gene mutations in RTKs may be a valuable prognostic factor in thymic squamous cell carcinoma.

Keywords: Next-generation sequence; Receptor tyrosine kinase; Targeted therapy; Thymic carcinoma; Thymic neuroendocrine tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Genes, Neoplasm / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation
  • Neuroendocrine Tumors / genetics*
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / pathology
  • Prognosis
  • Survival Rate
  • Thymoma / genetics*
  • Thymoma / mortality
  • Thymoma / pathology
  • Thymus Neoplasms / genetics*
  • Thymus Neoplasms / mortality
  • Thymus Neoplasms / pathology