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The Integrated Genomic Landscape of Thymic Epithelial Tumors.


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.

SUBMITTER: Radovich M 

PROVIDER: S-EPMC5994906 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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The Integrated Genomic Landscape of Thymic Epithelial Tumors.

Radovich Milan M   Pickering Curtis R CR   Felau Ina I   Ha Gavin G   Zhang Hailei H   Jo Heejoon H   Hoadley Katherine A KA   Anur Pavana P   Zhang Jiexin J   McLellan Mike M   Bowlby Reanne R   Matthew Thomas T   Danilova Ludmila L   Hegde Apurva M AM   Kim Jaegil J   Leiserson Mark D M MDM   Sethi Geetika G   Lu Charles C   Ryan Michael M   Su Xiaoping X   Cherniack Andrew D AD   Robertson Gordon G   Akbani Rehan R   Spellman Paul P   Weinstein John N JN   Hayes D Neil DN   Raphael Ben B   Lichtenberg Tara T   Leraas Kristen K   Zenklusen Jean Claude JC   Fujimoto Junya J   Scapulatempo-Neto Cristovam C   Moreira Andre L AL   Hwang David D   Huang James J   Marino Mirella M   Korst Robert R   Giaccone Giuseppe G   Gokmen-Polar Yesim Y   Badve Sunil S   Rajan Arun A   Ströbel Philipp P   Girard Nicolas N   Tsao Ming S MS   Marx Alexander A   Tsao Anne S AS   Loehrer Patrick J PJ  

Cancer cell 20180201 2


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  ...[more]

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