Artikel
Mutational signature in meningiomas defines tumour sub-classes with distinct risk-of-progression
Die genomische Signatur in Meningeomen definiert eine Subgruppe von Tumoren mit einem niedrigen Rezidivrisiko
Suche in Medline nach
Autoren
-
Insa Prilop
- Universitätsklinikum Carl Gustav Carus Dresden, Neurochirurgie, Dresden, Deutschland
-
Tristan Penson
- Massachusetts General Hospital, Department of Neurosurgery, Boston, MA, United States
-
Shilpa Tummala
- Massachusetts General Hospital, Department of Neurosurgery, Boston, MA, United States
-
Fred Barker
- Massachusetts General Hospital, Department of Neurosurgery, Boston, MA, United States
-
Priscilla Brastianos
- Massachusetts General Hospital, Division of Neuro-Oncology, Department of Neurology, Boston, MA, United States
-
Daniel Cahill
- Massachusetts General Hospital, Department of Neurosurgery, Boston, MA, United States
-
Tareq Juratli
- Universitätsklinikum Carl Gustav Carus Dresden, Neurochirurgie, Dresden, Deutschland; Massachusetts General Hospital, Department of Neurosurgery, Boston, MA, United States
| Veröffentlicht: | 26. Juni 2020 |
|---|
Gliederung
Text
Objective: Meningiomas are the most prevalent primary brain tumor. While most have a benign natural history, a subset has aggressive regrowth, resulting in high morbidity and mortality. Prior genomic characterization of meningiomas discovered mutations in TRAF7 (and the frequently co-mutated AKT1 and KLF4 genes) in lower-grade lesions, compared to the well-established NF2 alterations in these tumors. Here, we sought to assess the mutational signature of a cohort of progressive/high-grade meningiomas, with an aim to identify biomarkers associated with risk-of-progression.
Methods: We performed whole-exome sequencing (WES) in a cohort of 34 progressive/high-grade meningiomas samples from 24 patients, containing 10 matched samples. In addition, targeted sequencing was carried out in matched samples of an extended cohort, inclusive of the WES cohort, totaling 64 progressive meningiomas (n= 36 patients) to determine TRAF7, KLF4, AKT1 and TERT promoter (TERTp) hotspot mutations.
Results: We detected frequent genomic alterations that are known to be associated with an unfavorable prognosis in meningiomas: NF2 mutations (n=11, 45.8%), TERTp hotspot mutations (n=4, 17%) and DMD deletions (n=5, 21%). In contrast, none of the samples harbored a TRAF7, KLF4 or AKT1 mutation. Compared to pooled data from prior large-scale sequence surveys of meningiomas, which reveals a TRAF7 mutation rate of 23% (183 of 798 cases), the absence of TRAF7 mutation in our progressive/higher-grade cohort was highly significant (p=0.0002). Thus, we confirm that TRAF7 mutations identify a subclass of meningioma with a lower risk of progressive recurrence. In our cohort, TRAF7 mutations were mutually exclusive with NF2, TERTp and DMD alterations.
Conclusion: TRAF7 mutant meningiomas have a favorable natural history and therefore may require less intensive adjuvant treatment after initial surgical resection. This finding has important implications for clinical trials, as TRAF7 mutant meningioma patients are not likely to experience progressive disease during follow-up observation.
