Pathogenetic analysis of sinonasal teratocarcinosarcomas reveal actionable β-catenin overexpression and a β-catenin mutation

We read with great interest the article “Pathogenetic Analysis of Sinonasal Teratocarcinosarcomas Reveal Actionable β- Catenin Overexpression and a β-Catenin Mutation” by Birkeland et al.1 In the article, the authors performed targeted exome sequencing on an index Sinonasal Teratocarcinosarcoma (SNTCS) specimen and identified an activating mutation in the β-catenin gene (CTNNB1, c.134C > T, p.S45F). In addition, they confirmed β-catenin overexpression and nuclear localization via immunohistochemistry in the index tumor and in a subsequent case. Based on their findings, the authors suggested “a role for the Wnt/β-catenin pathway in SNTCS tumorigenesis,” postulated that “this mutation is a potential genetic driver mutation and an alluring prospect for treatment using inhibitors of the Wnt/β-catenin pathway” and underlined the importance “to screen for p.S45F mutations and other mutations/aberrations in β-catenin in other teratocarcinosarcoma specimens to identify if this is a common driver mutation in these tumors.”