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Rigshospitalet - a part of Copenhagen University Hospital
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TERT promoter mutations in primary and secondary WHO grade III meningioma

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PURPOSE: TERT promoter mutation (TERTpMut ) has a strong association to recurrence and has been suggested to act as a driver mutation for malignant transformation of WHO grade I and II meningiomas. TERTpMut has been investigated in selected high-grade meningioma samples. The existence of TERTpMut across recurrent tumors in a population-based cohort needs to be investigated in order to identify when TERTpMut emerges across recurrent samples and to validate prognostic impact among WHO grade III tumors.

METHODS: We gathered material from a consecutive single-center cohort of 40 patients with malignant meningioma (WHO grade III) treated between 2000 and 2018, including specimens from primary and secondary malignant meningiomas with the corresponding earlier benign specimens and later malignant recurrences. In total 107 tumor samples were studied by Sanger sequencing for TERT promoter mutational status.

RESULTS: Seven of 40 patients (17.5%) harbored TERTpMut thus validating the incidence of TERTpMut in previous non-population-based cohorts. In 6/7 patients, the TERTpMut was present at initial surgery (WHO grade I-III) while in one patient the TERTpMut was found de novo when the meningioma became malignant. The incidences were 2/1.000.000/year for TERTpMut WHO grade III meningioma and 8/1.000.000/year for TERTpwt WHO grade III meningioma in our catchment area. We found a 1.7 times higher recurrence rate (CI 95% 0.65-4.44) and a 2.5 higher mortality rate per 10 person-years (CI 95% 1.01-6.19) for TERTpMut compared to TERTpwt .

CONCLUSION: TERTpMut can occur independently of malignant progression in meningioma and was most often present from the first tumor sample across recurring tumors. TERTpMut in WHO grade III may represent a marker of an aggressive subset of tumors.

Original languageEnglish
JournalBrain pathology (Zurich, Switzerland)
Volume31
Issue number1
Pages (from-to)61-69
ISSN1015-6305
DOIs
Publication statusPublished - 31 Jan 2021

ID: 61346877