The Integrated Genomic Landscape of Thymic Epithelial Tumors

Cancer Cell. 2018 Feb 12;33(2):244-258.e10. doi: 10.1016/j.ccell.2018.01.003.


Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy.

Keywords: TCGA; autoimmunity; genomics; myasthenia gravis; proteomics; thymic carcinoma; thymic epithelial tumors; thymoma; transcriptomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Genomics
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasms, Glandular and Epithelial / genetics*
  • Thymoma / genetics*
  • Thymus Neoplasms / genetics*
  • Transcription Factors, TFII / genetics*
  • Young Adult


  • GTF2I protein, human
  • Transcription Factors, TFII

Supplementary concepts

  • Thymic epithelial tumor