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

• Verfasst von: Haller, Florian [VerfasserIn]
• Verfasst von: Bieg, Matthias [VerfasserIn]
• Verfasst von: Moskalev, Evgeny A. [VerfasserIn]
• Verfasst von: Barthelmeß, Sarah [VerfasserIn]
• Verfasst von: Geddert, Helene [VerfasserIn]
• Verfasst von: Boltze, Carsten [VerfasserIn]
• Verfasst von: Diessl, Nicolle [VerfasserIn]
• Verfasst von: Braumandl, Karin [VerfasserIn]
• Verfasst von: Brors, Benedikt [VerfasserIn]
• Verfasst von: Iro, Heinrich [VerfasserIn]
• Verfasst von: Hartmann, Arndt [VerfasserIn]
• Verfasst von: Wiemann, Stefan [VerfasserIn]
• Verfasst von: Agaimy, Abbas [VerfasserIn]
• Titel: Recurrent mutations within the amino-terminal region of β-catenin are probable key molecular driver events in sinonasal hemangiopericytoma
• Verf.angabe: Florian Haller, Matthias Bieg, Evgeny A. Moskalev, Sarah Barthelmeß, Helene Geddert, Carsten Boltze, Nicolle Diessl, Karin Braumandl, Benedikt Brors, Heinrich Iro, Arndt Hartmann, Stefan Wiemann, and Abbas Agaimy
• Jahr: 2015
• Jahr des Originals: 2014
• Umfang: 9 S.
• Teil: volume:185
• Teil: year:2015
• Teil: number:2
• Teil: month:02
• Teil: pages:563-571
• Teil: extent:9
• Fussnoten: Available online 4 December 2014 ; Gesehen am 25.03.2021
• Titel Quelle: Enthalten in: The American journal of pathology
• Ort Quelle: New York [u.a.] : Elsevier, 1925
• Jahr Quelle: 2015
• Band/Heft Quelle: 185(2015), 2 vom: Feb., Seite 563-571
• ISSN Quelle: 1525-2191
• DOI: doi:10.1016/j.ajpath.2014.10.019
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1556493339

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), 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.