Genomic and transcriptomic characterization of skull base chordoma

// Jason K. Sa 1, 2, 3 , In-Hee Lee 2, 3 , Sang Duk Hong 4 , Doo-Sik Kong 2, 3, 5 , Do-Hyun Nam 1, 2, 3, 5 1 Graduate School of Health Science & Technology, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University, Seoul, Korea 2 Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea 3 Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea 4 Department of Otorhinolaryngology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 5 Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Correspondence to: Do-Hyun Nam, email: nsnam@skku.edu Doo-Sik Kong, email: kds026@skku.edu Keywords: skull base chordoma, genomic characterization, transcriptomic characterization, gene fusion, T gene Received: September 26, 2016      Accepted: November 08, 2016      Published: November 25, 2016 ABSTRACT Skull base chordoma is a primary rare malignant bone-origin tumor showing relatively slow growth pattern and locally destructive lesions, which can only be characterized by histologic components. There is no available prognostic or therapeutic biomarker to predict clinical outcome or treatment response and the molecular mechanisms underlying chordoma development still remain unexplored. Therefore, we sought out to identify novel somatic variations that are associated with chordoma progression and potentially employed as therapeutic targets. Thirteen skull base chordomas were subjected for whole-exome and/or whole-transcriptome sequencing. In process, we have identified chromosomal aberration in 1p, 7, 10, 13 and 17q, high frequency of functional germline SNP of the T gene, rs2305089 ( P = 0.0038) and several recurrent alterations including MUC4 , NBPF1 , NPIPB15 mutations and novel gene fusion of SAMD5 - SASH1 for the first time in skull base chordoma.