Molecular Genetics of Thymic Carcinoma


Thymic carcinoma (TC) is a rare cancer with poor survival. Therapeutic regimen and drug clinical efficacy after failure of first‐line chemotherapy have not fully developed yet. Next‐generation sequencing studies were recently performed in patients with TC from Asian and Europe/US cohorts and reported genomic and epigenomic aberrations, including actionable aberrations for developing targeted personalised therapies. Some somatic variants, such as CYLD, TP53, HRAS and RB1, were commonly identified in both Asian and Europe/US cohorts, suggesting their contribution to thymic carcinogenesis. In addition to somatic mutations, epigenomic aberrations and gene rearrangements have been identified in TC. Mutational signature analysis revealed an accumulation of age‐related variants and DNA mismatch repair deficiency derived from TC development. The efforts to find novel actionable targets are continuing and immunotherapy for TC is investigated. Several clinical trials are currently underway to evaluate the therapeutic utility of immunotherapy for TC.

Key Concepts

  • Genomic and epigenomic aberrations in thymic carcinoma have been revealed.
  • Targeted therapy and immunotherapy for thymic carcinoma have been developed.
  • Thymic carcinoma is a rare cancer with poor survival.
  • Efficient therapeutic drugs after failure of the first‐line chemotherapy are required.
  • Genomic and epigenomic aberrations in thymic carcinoma have been revealed.
  • Targeted therapies for thymic carcinoma is being developed.
  • Efficacy of immunotherapy is expected for thymic carcinoma.

Keywords: thymic carcinoma; next‐generation sequencing; targeted therapy; immunotherapy

Figure 1. Genetic aberration profile of ten Japanese patients with thymic carcinoma. Average (a) and each (b) distribution of six categories of nucleotide substitution (C>A, C>G, C>T, T>A, T>C, T>G). Ti: nucleotide transition. Tv: nucleotide transversion.
Figure 2. Distribution of 96 nucleotide substitution spectra based on the neighbouring bases immediately 5′ and 3′ of the mutated base in the ten Japanese patients with thymic carcinoma.
Figure 3. Molecular aberration profile in ten Japanese patients with thymic carcinoma (TC). (a) Genes in the cancer gene census, chromatin remodelling genes (ch) and recurrently mutated genes in TC. Mutations registered in the COSMIC (Catalogue of Somatic Mutations in Cancer) database are marked by dots. (b) Genes with gain of expression. Focal copy number (CN) gains are indicated by upward arrows. (c) Genes with loss of expression. Truncating or splicing site mutation or focal CN losses are indicated by downward arrows. (d) Gene fusion detected in TC.


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Saito, Motonobu, Kono, Koji, and Kohno, Takashi(May 2019) Molecular Genetics of Thymic Carcinoma. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0028455]