Title

The Integrated Genomic Landscape of Thymic Epithelial Tumors.

Document Type

Article

Publication Date

2-12-2018

Keywords

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

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.

Clinical Institute

Cancer

Department

Oncology

Department

Institute for Systems Biology

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