Detection of novel fusion genes by next-generation sequencing-based targeted RNA sequencing analysis in adenoid cystic carcinoma of head and neck

• DOI: 10.1016/j.oooo.2021.03.020
• Publication Date: 2021-03-31T18:14:40Z
• Authors: Eri Shibata; Kei-ichi Morita; Kou Kayamori; Shoichiro Tange; Hiroki Shibata; Yosuke Harazono; Yasuyuki Michi; Tohru Ikeda; Hiroyuki Harada; Issei Imoto; Tetsuya Yoda
• Keywords: 0301 basic medicine; 03 medical and health sciences; Oncogene Proteins, Fusion; Sequence Analysis, RNA; Proto-Oncogene Proteins; Trans-Activators; High-Throughput Nucleotide Sequencing; Humans; Salivary Gland Neoplasms; Carcinoma, Adenoid Cystic; 3. Good health

Adenoid cystic carcinoma (AdCC) is a rare, indolent salivary gland tumor that is reported to be driven by fusion genes. However, MYB/MYBL1-NFIB fusions have been detected in <60% of all AdCC cases and the oncogenic driver mutations in approximately 40% of AdCC remain unknown. Our aim was to identify novel gene fusions in AdCC.We investigated 20 AdCC cases using a targeted RNA sequencing panel to identify gene fusions and performed quantitative real-time reverse transcription polymerase chain reaction to assess MYB, MYBL1, and NFIB expression levels.A total of 36 fusion transcripts in 15 cases were detected and validated by Sanger sequencing. The MYB-NFIB and MYBL1-NFIB fusion genes were detected in 9 and 3 cases, respectively, in a mutually exclusive manner. Furthermore, novel gene fusions, namely, NFIB-EPB41L2, MAP7-NFIB, NFIB-MCMDC2, MYBL1-C8orf34, C8orf34-NFIB, and NFIB-CASC20, were identified. Among them, NFIB-EPB41L2 and NFIB-MCMDC2 are thought to activate MYB and MYBL1 expression, respectively, through the insertion of a genomic segment in proximity to MYB and MYBL1 genes, respectively.Six novel gene fusions other than MYB/MYBL1-NFIB were identified. The detection of novel fusion genes and investigation of the molecular mechanism will contribute to the development of novel molecular targeted therapies for this disease.