Characterization of genetic aberrations in a single case of metastatic thymic adenocarcinoma

BMC Cancer

Sehhoon Park¹  Se-Hoon Lee¹  Yeonghun Lee²  Hyunju Lee² 

[1] Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Hospital;School of Electrical Engineering and Computer Science, Gwangju Institute of Science and Technology;

关键词: Thymic adenocarcinoma;    Thymic epithelial tumors;    Whole exome sequencing;    Somatic mutations;    Somatic copy number alterations;   

DOI  :  10.1186/s12885-017-3282-9

来源: DOAJ

【 摘 要 】

Abstract Background Thymic adenocarcinoma is an extremely rare subtype of thymic epithelial tumors. Due to its rarity, there is currently no sequencing approach for thymic adenocarcinoma. Methods We performed whole exome and transcriptome sequencing on a case of thymic adenocarcinoma and performed subsequent validation using Sanger sequencing. Results 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. Conclusion Thymic adenocarcinoma shows highly malignant characteristics with alterations in several cancer-related genes.

【 授权许可】

Unknown