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Telomerase promoter mutations and copy number alterations in solitary fibrous tumours
  1. Yingbo Lin1,
  2. Nelly Seger1,
  3. Panagiotis Tsagkozis2,3,
  4. Asle C Hesla2,3,
  5. Mehran Ghaderi1,4,
  6. Yi Chen1,
  7. Monika Ehnman1,
  8. Dudi Warsito1,
  9. Johan Wejde1,4,
  10. Olle Larsson1,4,
  11. Felix Haglund1,4
  1. 1Department of Oncology–Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
  2. 2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  3. 3Department of Orthopedic Surgery, Karolinska University Hospital Solna, Stockholm, Sweden
  4. 4Department of Clinical Pathology and Cytology, Karolinska University Hospital Solna, Stockholm, Sweden
  1. Correspondence to Dr Felix Haglund, Karolinska University Hospital Solna, Stockholm 17176, Sweden; Felix.Haglund{at}ki.se

Abstract

Aims Solitary fibrous tumour (SFT) is an infrequently metastasising mesenchymal tumour defined by the NAB2–STAT6 fusion gene. Activating mutations in the telomerase reverse transcriptase (hTERT) gene promoter has been reported to associate with adverse patient outcome in SFTs.

Methods We analysed the hTERT 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%) hTERT 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. hTERT copy number gain was seen in 11/28 hTERT promoter wild-type cases.

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

  • sarcomas
  • soft tissue tumours
  • cancer genetics

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Footnotes

  • Handling editor Runjan Chetty.

  • Contributors Conception or design of the work: YL, OL, FH. Data collection: YL, NS, PT, ACH, MG, YC, ME, DW, FH. Data analysis and interpretation: JW, PT, FH. Drafting the article: YL, FH. Critical revision of the article: NS, PT, ACH, MG, YC, ME, DW, JW, OL.

  • Funding This study was supported by the Swedish Cancer Society, the Swedish Research Council, the Cancer Society in Stockholm, the Swedish Childhood Cancer Foundation, the Stockholm County Council and Karolinska Institutet.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Regionala Etikprövningsnämnden Stockholm.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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