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Abstract：
Thymic adenocarcinoma is an extremely rare subtype of thymic epithelial tumors. Due to its rarity, there is currently no sequencing approach for thymic adenocarcinoma.
We performed whole exome and transcriptome sequencing on a case of thymic adenocarcinoma and performed subsequent validation using Sanger sequencing.
The case of thymic adenocarcinoma showed aggressive behaviors with systemic bone metastases. We identified a high incidence of genetic aberrations, which included somatic mutations in RNASEL, PEG10, TNFSF15, TP53, TGFB2, and FAT1. Copy number analysis revealed a complex chromosomal rearrangement of chromosome 8, which resulted in gene fusion between MCM4 and SNTB1 and dramatic amplification of MYC and NDRG1. Focal deletion was detected at human leukocyte antigen (HLA) class II alleles, which was previously observed in thymic epithelial tumors. We further investigated fusion transcripts using RNA-seq data and found an intergenic splicing event between the CTBS and GNG5 transcript. Finally, enrichment analysis using all the variants represented the immune system dysfunction in thymic adenocarcinoma.
Thymic adenocarcinoma shows highly malignant characteristics with alterations in several cancer-related genes.
We performed whole exome and transcriptome sequencing on a case of thymic adenocarcinoma and performed subsequent validation using Sanger sequencing.
The case of thymic adenocarcinoma showed aggressive behaviors with systemic bone metastases. We identified a high incidence of genetic aberrations, which included somatic mutations in RNASEL, PEG10, TNFSF15, TP53, TGFB2, and FAT1. Copy number analysis revealed a complex chromosomal rearrangement of chromosome 8, which resulted in gene fusion between MCM4 and SNTB1 and dramatic amplification of MYC and NDRG1. Focal deletion was detected at human leukocyte antigen (HLA) class II alleles, which was previously observed in thymic epithelial tumors. We further investigated fusion transcripts using RNA-seq data and found an intergenic splicing event between the CTBS and GNG5 transcript. Finally, enrichment analysis using all the variants represented the immune system dysfunction in thymic adenocarcinoma.
Thymic adenocarcinoma shows highly malignant characteristics with alterations in several cancer-related genes.
摘要：
胸腺腺癌是一种极为罕见的胸腺上皮肿瘤亚型。由于它的稀有性,目前没有胸腺腺癌的测序方法。
我们对一例胸腺腺癌进行了全外显子组和转录组测序，并使用Sanger测序进行了后续验证。
胸腺腺癌表现为侵袭性行为，伴全身性骨转移。我们发现遗传畸变的发生率很高，其中包括RNASEL的体细胞突变，PEG10、TNFSF15、TP53、TGFB2和FAT1。拷贝数分析显示8号染色体的复杂染色体重排，导致MCM4和SNTB1之间的基因融合以及MYC和NDRG1的急剧扩增。在人类白细胞抗原（HLA）II类等位基因中检测到局灶性缺失，以前在胸腺上皮肿瘤中观察到。我们使用RNA-seq数据进一步研究了融合转录本，发现了CTBS和GNG5转录本之间的基因间剪接事件。最后,使用所有变体的富集分析代表胸腺腺癌的免疫系统功能障碍。
胸腺腺癌表现出高度恶性特征，并在几个癌症相关基因中发生改变。
我们对一例胸腺腺癌进行了全外显子组和转录组测序，并使用Sanger测序进行了后续验证。
胸腺腺癌表现为侵袭性行为，伴全身性骨转移。我们发现遗传畸变的发生率很高，其中包括RNASEL的体细胞突变，PEG10、TNFSF15、TP53、TGFB2和FAT1。拷贝数分析显示8号染色体的复杂染色体重排，导致MCM4和SNTB1之间的基因融合以及MYC和NDRG1的急剧扩增。在人类白细胞抗原（HLA）II类等位基因中检测到局灶性缺失，以前在胸腺上皮肿瘤中观察到。我们使用RNA-seq数据进一步研究了融合转录本，发现了CTBS和GNG5转录本之间的基因间剪接事件。最后,使用所有变体的富集分析代表胸腺腺癌的免疫系统功能障碍。
胸腺腺癌表现出高度恶性特征，并在几个癌症相关基因中发生改变。
