The Integrated Genomic Landscape of Thymic Epithelial Tumors

The Cancer Genome Atlas Network

Research output: Contribution to journalArticlepeer-review

243 Scopus citations

Abstract

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. Radovich et al. perform multi-platform analyses of thymic epithelial tumors. They identify high prevalence of GTF2I mutations and enrichment of mutations in HRAS, NRAS, and TP53 and link overexpression of muscle autoantigens and increased aneuploidy in thymoma and patients’ risk of having myasthenia gravis.

Original languageEnglish (US)
Pages (from-to)244-258.e10
JournalCancer cell
Volume33
Issue number2
DOIs
StatePublished - Feb 12 2018

Keywords

  • TCGA
  • autoimmunity
  • genomics
  • myasthenia gravis
  • proteomics
  • thymic carcinoma
  • thymic epithelial tumors
  • thymoma
  • transcriptomics

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

MD Anderson CCSG core facilities

  • Bioinformatics Shared Resource

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