Whole-transcriptome analysis of chordoma of the skull base.

Fourteen skull base chordoma specimens and three normal specimens were microdissected from paraffin-embedded tissue. Pools of RNA from highly enriched preparations of these cell types were subjected to expression profiling using whole-transcriptome shotgun sequencing. Using strict criteria, 294 differentially expressed transcripts were found, with 28 % upregulated and 72 % downregulated. The transcripts were annotated using NCBI Entrez Gene and computationally analyzed with the Ingenuity Pathway Analysis program. From these significantly changed expressions, the analysis identified 222 cancer-related transcripts. These 294 differentially expressed genes and non-coding RNA transcripts provide here a set to specifically define skull base chordomas and to identify novel and potentially important targets for diagnosis, prognosis, and therapy of this cancer. Significance Genomic profiling to subtype skull base chordoma reveals potential candidates for specific biomarkers, with validation by IHC for selected candidates. The highly expressed developmental genes T, LMX1A, ZIC4, LHX4, and HOXA1 may be potential drivers of this disease.