Identification of Novel Germline and Tumor-Specific Nucleotide Variants and Copy Number Variation in Clival Chordomas by Exome Sequencing

Introduction: Chordoma is a rare, locally aggressive tumor with high recurrence rates. Available treatments are restricted to surgery and radiation. Our limited understanding of the tumor's underlying molecular pathophysiology compromises early prognosis and precludes the use of targeted molecular therapies. Methods: We performed high resolution, paired-end, exome sequencing (Life Technologies SOLiD 5,500; > 100 times base depth) of DNA from five primary clival chordomas and matched blood of patients undergoing endoscopic endonasal surgery. BAM (Binary Alignment tab delimited) files were mapped to HG19 (Human Genome version 19), aligned (Burrows-Wheeler & Smith-Waterman algorithms) and analyzed using a battery of algorithms. Single nucleotide variants (polymorphisms:SNPs; substitutions:SUBs) and insertions/deletions (INDELs: