Thymic epithelial tumors (TET) including thymomas and thymic carcinomas are rare, but they are common primary tumors in the anterior mediastinum. The etiology and tumorigenesis of TET remain unclear. To better understand the novel aberrations of this rare tumor and provide more significant mutation sites for targeted therapy, we performed next-generation sequencing detection on 55 patients with TET. Our results showed that most genes in 12 core pathways harbored aberrations of indeterminate potential. In 4 genes (ARID1A, KMT2C, TGFBR2 and MAP3K1), the indel frequency was above 90%. Dozens of genes, including TGFBR2, KMT2C, PRKDC, ATR, CHD2, SDHA, KDM5A, CHEK1, MSH6 and POLE, possessed frameshift indel with different frequencies in different hotspot sites, which could be the new targets of therapy for TET. For the first time, we revealed a strong correlation between the tumor mutational burden and single nucleotide variations, but not frameshift, on DNA mismatch repair gene MSH6 in TET.

中文翻译：

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胸腺上皮肿瘤的下一代测序发现了新的基因组畸变位点和TMB和MSH6单核苷酸变异之间的强相关性。

胸腺上皮肿瘤（TET）包括胸腺瘤和胸腺癌很少见，但它们是前纵隔常见的原发肿瘤。TET的病因和致瘤作用仍不清楚。为了更好地了解这种罕见肿瘤的新畸变并为靶向治疗提供更多重要的突变位点，我们对55名TET患者进行了新一代测序检测。我们的结果表明，12条核心途径中的大多数基因都具有不确定的潜在畸变。在4个基因（ARID1A，KMT2C，TGFBR2和MAP3K1）中，插入缺失频率高于90％。TGFBR2，KMT2C，PRKDC，ATR，CHD2，SDHA，KDM5A，CHEK1，MSH6和POLE等数十个基因在不同热点位置具有不同频率的移码插入缺失，这可能是TET治疗的新靶标。首次，