HTERT promoter mutations in chondrosarcomas associate with progression and disease-related mortality. (December 2018)

• Record Type: Journal Article
• Authors: Lin, Yingbo; Seger, Nelly; Chen, Yi; Hesla, Asle; Wejde, Johan; Ghaderi, Mehran; Tsagkozis, Panagiotis; Larsson, Olle; Haglund, Felix
• Is Part Of: Modern pathology. Volume 31:Number 12(2018)
• Page Start: 1834
• Page End: 1841
• Publication Date: 2018-12
• Subjects: Pathology -- Periodicals; Diagnosis, Laboratory -- Periodicals; Pathologie -- Périodiques; Diagnostics biologiques -- Périodiques; Diagnosis, Laboratory; Pathology; Pathology -- Abstracts; Pathology -- Periodicals; Periodicals; Electronic journals; 616.07
• DOI: 10.1038/s41379-018-0098-3
• Languages: English
• ISSNs: 0893-3952

Abstract

Abstract Chondrosarcomas are malignant skeletal tumors with chondroid differentiation. Prognosis is largely dependent on histological grading, which suffer from significant interobserver variability. Telomerase activity and abundanttelomerase reverse transcriptase (hTERT ) expression has previously been associated with chondrosarcoma grade and metastasis. We therefore analyzed thehTERT promoter in clinicopathologically well-characterized chondrosarcomas (grade 1–3) from 87 patients. Using Sanger sequencing we identified an activating −124 C > T mutation in 23 cases (26%). Promoter mutations were significantly associated with increased histological grade (8% of grade 1, 32% of grade 2 and 46% of grade 3, P = 0.002), suggesting a role in tumor progression. In four chondrosarcomas where the histopathological grade was heterogenous, thehTERT mutation was only identified in the higher-grade areas. Additionally, hTERT promoter mutations were significantly associated with worse metastasis-free survival (P = 0.018), chondrosarcoma-specific survival (P = 0.022) and older patient age (P = 0.003). These data suggest thathTERT promoter mutations are common in high grade conventional chondrosarcomas. Granted that additional studies can confirm these findings;hTERT promoter analysis could potentially serve as an adjuvant prognostic marker in routine chondrosarcoma grading. This study reinforces the rationale of telomerase targeted therapy in a subset of chondrosarcomas.