BACKGROUND: Spinal chordomas, a sub-type of primary spinal column malignancies (PSCM), are rare tumors with poor prognosis and limited understanding of the molecular drivers of neoplasia.
METHODS: Study design was a retrospective review of prospectively collected data with cross-sectional survival. Archived paraffin embedded pathologic specimens were collected for 133 patients from 6 centers within Europe and North America between 1987 and 2012. Tumor DNA was extracted and the hTERT promoter was sequenced. The hTERT mutational status was correlated to overall survival (OS) and time to first local recurrence.
RESULTS: Ninety-two chordomas, twenty-six chondrosarcomas, seven osteosarcomas, three Ewing's sarcomas, and five other malignant spinal tumors were analyzed. Median OS following surgery was 5.8 years (95% CI: 4.6 to 6.9) and median time to first local recurrence was 3.9 years (95% CI: 2.5 to 6.7). Eight chordomas, two chondrosarcomas, one Ewing's sarcoma, and one other malignant spinal tumor harbored either a C228T or C250T mutation in the hTERT promoter. In the overall cohort, all patients with hTERT mutation were alive at ten years postoperative with a median overall survival (OS) of 5.1 years (95% CI: 4.5 to 6.6)(p=0.03). hTERT promoter mutation was observed in 8.7% of spinal chordomas and 100% of chordoma patients harboring the mutation were alive at ten years postoperative compared to 67% patients without the mutation (p=0.05).
CONCLUSIONS: We report for the first time that hTERT promoter mutations C228T and C250T are present in approximately 8.7% of spinal chordomas. The presence of hTERT mutations conferred a survival benefit and could potentially be a valuable positive prognostic molecular marker in spinal chordomas.
- promoter mutation
- primary spinal column malignancy