Recurrent Mutations within the Amino-Terminal Region of ?-Catenin Are Probable Key Molecular Driver Events in Sinonasal Hemangiopericytoma

Haller F, Bieg M, Moskalev E, Barthelmeß S, Geddert H, Boltze C, Diessl N, Braumandl K, Brors B, Iro H, Hartmann A, Wiemann S, Agaimy A (2015)

Publication Type: Journal article

Publication year: 2015

Journal

American Journal of Pathology American Society for Investigative Pathology (ASIP)

Book Volume: 185

Pages Range: 563-71

Journal Issue: 2

DOI: 10.1016/j.ajpath.2014.10.019

Abstract

Sinonasal hemangiopericytoma (SN-HPC) is an uncommon, site-specific, low-grade mesenchymal neoplasm of probable perivascular myoid cell origin. In contrast to solitary fibrous tumors of soft tissue and sinonasal tract origin, SN-HPCs were recently shown to lack recurrent NAB2-STAT6 fusion variants. Other molecular alterations known to occur in some of soft tissue perivascular myoid cell neoplasms were also absent in SN-HPC; thus, the molecular pathogenesis of SN-HPCs remained unknown. Guided by whole-genome sequencing combined with RNA sequencing of an index case, we analyzed a total of six SN-HPCs for mutations within the amino-terminal region of the gene CTNNB1 (cadherin-associated protein), ? 1, 88 kDa, encoding ?-catenin. All six cases showed missense mutations, with amino acid substitutions clustering at positions 33 to 45, corresponding to the recognition site of the ?-catenin destruction complex. Similar CTNNB1 mutations have been described in a variety of epithelial and mesenchymal neoplasms. These mutations prevent ?-catenin phosphorylation and proteasomal degradation but promote its nuclear accumulation and subsequent increased transcription of Wingless-related integration site target genes. Consistent with these molecular findings, ?-catenin IHC showed consistent diffuse and strong nuclear staining of the tumor cells in all six SN-HPCs. Our results highlight, for the first time, CTNNB1 mutations as the likely initiating molecular events driving SN-HPC tumorigenesis, which places SN-HPC among the growing family of ?-catenin-driven mesenchymal neoplasms.

Authors with CRIS profile

Evgeny Moskalev Institute of Pathology Sarah Barthelmeß Institute of Pathology Karin Braumandl Professur für Diagnostische Molekularpathologie Heinrich Iro Lehrstuhl für Hals-, Nasen- und Ohrenheilkunde Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) St Vincent's Hospital AU Australia (AU) SRH Wald-Klinikum Gera DE Germany (DE)

How to cite

APA:

Haller, F., Bieg, M., Moskalev, E., Barthelmeß, S., Geddert, H., Boltze, C.,... Agaimy, A. (2015). Recurrent Mutations within the Amino-Terminal Region of ?-Catenin Are Probable Key Molecular Driver Events in Sinonasal Hemangiopericytoma. American Journal of Pathology, 185(2), 563-71. https://doi.org/10.1016/j.ajpath.2014.10.019

MLA:

Haller, Florian, et al. "Recurrent Mutations within the Amino-Terminal Region of ?-Catenin Are Probable Key Molecular Driver Events in Sinonasal Hemangiopericytoma." American Journal of Pathology 185.2 (2015): 563-71.

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