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.

中文翻译：

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胸腺上皮肿瘤的综合基因组景观。

胸腺上皮肿瘤（TETs）是最罕见的成人恶性肿瘤之一。在TET中，胸腺瘤是最主要的，其特点是与自身免疫性疾病有独特的联系，其次是胸腺癌，这种病较不常见，但在临床上更具侵略性。通过对117种TET进行多平台组学分析，我们定义了这些肿瘤的四个亚型，这些亚型由基因组标志以及与生存和世界卫生组织组织学亚型的关联定义。我们进一步证明了胸腺瘤特异性突变致癌基因GTF2I的显着流行，并探讨了其在多平台分析中的生物学作用。我们进一步观察到HRAS，NRAS和TP53中突变的富集。最后，我们确定了胸腺瘤与自身免疫性疾病重症肌无力之间的分子联系，其特征是肌肉自身抗原的肿瘤过度表达，