Pathogenetic Analysis of Sinonasal Teratocarcinosarcomas Reveal Actionable β-catenin Overexpression and a β-catenin Mutation

Andrew C. Birkeland, Sarah J. Burgin, Megan Yanik, Megan V. Scott, Carol R. Bradford, Jonathan B. McHugh, Scott A. McLean, Stephen E. Sullivan, Jacques E. Nor, Erin L. McKean, J. Chad Brenner

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Objective Sinonasal teratocarcinosarcomas are rare, aggressive tumors of the skull base. Treatment options are limited and outcomes are poor. Little is known in regard to the genetic factors regulating these tumors. Characterization of actionable molecular alterations in these tumors could provide potentially successful therapeutic options. Methods We performed targeted exome sequencing on an index sinonasal teratocarcinosarcoma specimen to identify potential driver mutations. We performed immunohistochemical stains for β-catenin on paraffin-embedded tissue on the index tumor and a subsequent teratocarcinosarcoma. Online databases of cancer mutations (Catalogue of Somatic Mutations in Cancer and The Cancer Genome Atlas) were accessed. Results We identified an activating p.S45F mutation in β-catenin in our index sinonasal teratocarcinosarcoma. This mutation results in constitutive signaling in the Wnt/β-catenin pathway. We confirmed β-catenin overexpression and nuclear localization via immunohistochemistry in the index tumor and a second patient. The p.S45F activating mutation was found in a variety of solid tumors, and accounts for 3.3 to 10.4% of all known β-catenin mutations. Conclusion We identified a potential driver mutation in β-catenin in a sinonasal teratocarcinosarcoma, resulting in β-catenin overexpression. These findings suggest a role for the Wnt/β-catenin pathway in sinonasal teratocarcinosarcoma tumorigenesis and a role for anti-β-catenin targeted therapy.

Original languageEnglish (US)
Pages (from-to)346-352
Number of pages7
JournalJournal of Neurological Surgery, Part B: Skull Base
Issue number4
StatePublished - Aug 1 2017
Externally publishedYes


  • CTNNB1
  • pathogenetics
  • sinonasal teratocarcinosarcoma
  • teratocarcinosarcoma
  • Wnt
  • β-catenin

ASJC Scopus subject areas

  • Clinical Neurology


Dive into the research topics of 'Pathogenetic Analysis of Sinonasal Teratocarcinosarcomas Reveal Actionable β-catenin Overexpression and a β-catenin Mutation'. Together they form a unique fingerprint.

Cite this