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
Book Volume: 185
Pages Range: 563-71
Journal Issue: 2
DOI: 10.1016/j.ajpath.2014.10.019
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.
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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