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

• Published in: Journal of neurological surgery. Part B, Skull base Vol. 78; no. 4; pp. 346 - 352
• Main Authors: Birkeland, Andrew C., Burgin, Sarah J., Yanik, Megan, Scott, Megan V., Bradford, Carol R., McHugh, Jonathan B., McLean, Scott A., Sullivan, Stephen E., Nor, Jacques E., McKean, Erin L., Brenner, J. Chad
• Format: Journal Article
• Language: English
• Published: Stuttgart · New York Georg Thieme Verlag KG 01.08.2017
• Subjects: Original; Original Article; teratocarcinosarcoma; β-catenin; sinonasal teratocarcinosarcoma; pathogenetics; Wnt; CTNNB1
• ISSN: 2193-6331; 2193-634X
• DOI: 10.1055/s-0037-1601320

Abstract 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.