胸腺癌的综合基因组景观。
The Integrated Genomic Landscape of Thymic Epithelial Tumors.
机构信息
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA.
MD Anderson Cancer Center, Houston, TX 77030, USA.
出版信息
Cancer Cell. 2018 Feb 12;33(2):244-258.e10. doi: 10.1016/j.ccell.2018.01.003.
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.
摘要
胸腺上皮肿瘤（TETs）是最罕见的成人恶性肿瘤之一。在 TETs 中，胸腺瘤最为常见，其特征是与自身免疫性疾病有独特的关联，其次是胸腺癌，虽然不太常见，但更具临床侵袭性。我们对 117 例 TETs 进行了多平台组学分析，根据基因组特征和与生存以及世界卫生组织组织学亚型的关联，定义了这些肿瘤的四个亚型。我们进一步证明了胸腺瘤特异性突变致癌基因 GTF2I 的明显流行，并探讨了其对多平台分析的生物学影响。我们还观察到 HRAS、NRAS 和 TP53 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，其特征是肿瘤过度表达肌肉自身抗原和非整倍体增加。
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