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Molecular defects in BRAF wild-type ameloblastomas and craniopharyngiomas—differences in mutation profiles in epithelial-derived oropharyngeal neoplasms

Abstract

The aim of this study was to evaluate the mutation profile of BRAF wild-type craniopharyngiomas and ameloblastomas. Pre-screening by immunohistochemistry and pyrosequencing for identifying BRAF wild-type tumors was performed on archived specimens of ameloblastic tumors (n = 20) and craniopharyngiomas (n = 62). Subsequently, 19 BRAF wild-type tumors (nine ameloblastic tumors and ten craniopharyngiomas) were analyzed further using next-generation sequencing (NGS) targeting hot spot mutations of 22 cancer-related genes. Thereby, we found craniopharyngiomas mainly CTNNB1 mutated (8/10), including two FGFR3/CTNNB1-double mutated tumors. Ameloblastic tumors were often FGFR2 mutated (4/9; including one FGFR2/TP53/PTEN-triple mutated case) and rarely CTNNB1/TP53-double mutated (1/9) and KRAS-mutated (1/9). In the remaining samples, no mutation could be detected in the 22 genes under investigation. In conclusion, mutation profiles of BRAF wild-type craniopharyngiomas and ameloblastomas share mutations of FGFR genes and have additional mutations with potential for targeted therapy.

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Funding

This study was funded by “Niedersächsische Krebsgesellschaft, e.V.” (Hannover, DE).

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Correspondence to Kais Hussein.

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The authors declare that they have no conflict of interest.

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Bartels, S., Adisa, A., Aladelusi, T. et al. Molecular defects in BRAF wild-type ameloblastomas and craniopharyngiomas—differences in mutation profiles in epithelial-derived oropharyngeal neoplasms. Virchows Arch 472, 1055–1059 (2018). https://doi.org/10.1007/s00428-018-2323-3

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Keywords

  • BRAF
  • CTNNB1, FGFR
  • Ameloblastoma
  • Ameloblastic carcinoma
  • Craniopharyngioma