Prognostic significance of human telomerase reverse transcriptase promoter region mutations C228T and C250T for overall survival in spinal chordomas

Spinal chordomas, a subtype of primary spinal column malignancies (PSCM), are rare tumors with poor prognosis, and we have limited understanding of the molecular drivers of neoplasia. 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 human telomerase reverse transcriptase (hTERT) promoter was sequenced. The hTERT mutational status was correlated with overall survival (OS) and time to first local recurrence. Ninety-two chordomas, 26 chondrosarcomas, 7 osteosarcomas, 3 Ewing's sarcomas, and 5 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, 2 chondrosarcomas, 1 Ewing's sarcoma, and 1 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 10 years postoperative with a median 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 10 years postoperative compared with 67% patients without the mutation (P = 0.05). 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.