J Neurol Surg B 2016; 77 - A093
DOI: 10.1055/s-0036-1579881

Pathogenetic Analysis of Sinonasal Teratocarcinosarcomas Reveal Beta-catenin Overexpression and an Actionable Beta-catenin Mutation

Andrew C. Birkeland 1, Sarah Burgin 1, Jacques E. Nor 1, Jonathan B. McHugh 1, Scott A. McLean 1, Erin L. McKean 1, Chad Brenner 1
  • 1University of Michigan, Ann Arbor, Michigan, United States

Background: Sinonasal teratocarcinosarcomas are rare, aggressive tumors of the skull base. Treatment options are limited to surgery and radiation, and outcomes are poor, with high rates of recurrence and metastasis. Little is known in regards to the genetic factors regulating these tumors. Characterization of actionable molecular alterations in these tumors could provide an alternate, potentially successful, therapeutic option.

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 (COSMIC, TCGA) were accessed to identify mutations in β catenin-catenin.

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. Immunohistochemistry of a sinonasal teratocarcinosarcoma from a second patient also demonstrated intense β-catenin overexpression and nuclear localization. The pS45F activating mutation was found in a variety of solid tumors, and accounts for 3.3–10.4% of all known β-catenin mutations.

Conclusions: 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. This is a potentially targetable mutation as β-catenin inhibitors are in early clinical trials. Further studies into response of sinonasal teratocarcinosarcomas to β-catenin inhibitors may provide insight into targeted therapy for these difficult-to-treat tumors.