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

doi:10.1055/s-0037-1601320

Journal of Neurological Surgery Part B: Skull Base, Table of Contents

J Neurol Surg B Skull Base 2017; 78(04): 346-352
DOI: 10.1055/s-0037-1601320

Original Article

Georg Thieme Verlag KG Stuttgart · New York

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

Authors

Andrew C. Birkeland^*

¹Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
Sarah J. Burgin^*

¹Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
Megan Yanik

¹Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
Megan V. Scott

¹Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
Carol R. Bradford

¹Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States

²Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan, United States
Jonathan B. McHugh

³Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States
Scott A. McLean

¹Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
Stephen E. Sullivan

⁴Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
Jacques E. Nor

¹Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
Erin L. McKean^†

¹Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
J. Chad Brenner^†

¹Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States

²Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan, United States

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.

Keywords

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

Full Text

References

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Supplementary Material

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