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Haller, Florian [Author]; Bieg, Matthias [Author]; Moskalev, Evgeny A. [Author]; Barthelmeß, Sarah [Author]; Geddert, Helene [Author]; Boltze, Carsten [Author]; Diessl, Nicolle [Author]; Braumandl, Karin [Author]; Brors, Benedikt [Author]; Iro, Heinrich [Author]; Hartmann, Arndt [Author]; Wiemann, Stefan [Author]; Agaimy, Abbas [Author]

Recurrent mutations within the amino-terminal region of β-catenin are probable key molecular driver events in sinonasal hemangiopericytoma

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  • Media type: E-Article
  • Title: Recurrent mutations within the amino-terminal region of β-catenin are probable key molecular driver events in sinonasal hemangiopericytoma
  • Contributor: Haller, Florian [VerfasserIn]; Bieg, Matthias [VerfasserIn]; Moskalev, Evgeny A. [VerfasserIn]; Barthelmeß, Sarah [VerfasserIn]; Geddert, Helene [VerfasserIn]; Boltze, Carsten [VerfasserIn]; Diessl, Nicolle [VerfasserIn]; Braumandl, Karin [VerfasserIn]; Brors, Benedikt [VerfasserIn]; Iro, Heinrich [VerfasserIn]; Hartmann, Arndt [VerfasserIn]; Wiemann, Stefan [VerfasserIn]; Agaimy, Abbas [VerfasserIn]
  • imprint: 2015
  • Published in: The American journal of pathology ; 185(2015), 2 vom: Feb., Seite 563-571
  • Language: English
  • DOI: 10.1016/j.ajpath.2014.10.019
  • ISSN: 1525-2191
  • Identifier:
  • Origination:
  • Footnote: Available online 4 December 2014
  • Description: 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), β 1, 88 kDa, encoding β-catenin. All six cases showed missense mutations, with amino acid substitutions clustering at positions 33 to 45, corresponding to the recognition site of the β-catenin destruction complex. Similar CTNNB1 mutations have been described in a variety of epithelial and mesenchymal neoplasms. These mutations prevent β-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, β-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 β-catenin-driven mesenchymal neoplasms.
  • Access State: Open Access