Telomerase promoter mutations and copy number alterations in solitary fibrous tumours.

AIMS

Solitary fibrous tumour (SFT) is an infrequently metastasising mesenchymal tumour defined by the fusion gene. Activating mutations in the () gene promoter has been reported to associate with adverse patient outcome in SFTs.

METHODS

We analysed the gene for promoter mutations and copy number alterations in 43 primary extrameningeal SFTs (9 malignant and 34 benign tumours according to WHO 2013 criteria), six local recurrences and three metastatic lesions.

RESULTS

Activating -124 C>T (n=12) or -148 C>T (n=2) mutations were found in 33% of the tumours and associated with older age (P=0.006), necrosis (P=0.009), higher mitotic rate (P=0.003), nuclear atypia (P=0.002), malignant histological diagnosis (P=0.04) and worse progression-free survival (P=0.023). We also observed frequent (24%) promoter mutations in histologically benign tumours without metastasis (mean follow-up >9 years), and in 14%-18% of low-risk SFTs as determined by three risk-stratification models. Mutations were seen in 2/6 metastatic tumours and metastatic lesions. copy number gain was seen in 11/28 promoter wild-type cases.

CONCLUSIONS

Activating promoter mutations associate with aggressive histopathological features, indicating a role in tumour progression. Given the comparatively high prevalence of promoter mutations in low-risk and non-metastasising lesions, further studies are required to clarify the prognostic value of promoter analysis before implementing the analysis in clinical diagnostics.