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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

Andrew C. Birkeland   *
1   Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
,
Sarah J. Burgin   *
1   Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
,
Megan Yanik
1   Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
,
Megan V. Scott
1   Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
,
Carol R. Bradford
1   Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
2   Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan, United States
,
Jonathan B. McHugh
3   Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States
,
Scott A. McLean
1   Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
,
Stephen E. Sullivan
4   Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
,
Jacques E. Nor
1   Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
,
Erin L. McKean   †
1   Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
,
J. Chad Brenner   †
1   Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States
2   Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan, United States
› Author Affiliations
Further Information

Publication History

20 November 2016

12 February 2017

Publication Date:
27 March 2017 (online)

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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

* These authors contributed equally to this work.


† These are cosenior authors.


Supplementary Material

 

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