Lipomatous Solitary Fibrous Tumors Harbor Rare NAB2-STAT6 Fusion Variants and Show Up-Regulation of the Gene PPARG, Encoding for a Regulator of Adipocyte Differentiation

Haller F, Schlieben LD, Ferrazzi F, Michal M, Stöhr R, Moskalev E, Bieg M, Bovée JV, Ströbel P, Ishaque N, Grützmann R, Meidenbauer N, Eils R, Wiemann S, Hartmann A, Michal M, Agaimy A (2021)

Publication Type: Journal article

Publication year: 2021

Journal

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

DOI: 10.1016/j.ajpath.2021.03.012

Abstract

Solitary fibrous tumors (SFTs) harbor activating NAB2-STAT6 gene fusions. Different variants of the NAB2-STAT6 gene fusion have been associated with distinct clinicopathologic features. Lipomatous SFTs are a morphologic variant of SFTs, characterized by a fat-forming tumor component. Our aim was to evaluate NAB2-STAT6 fusion variants and to further study the molecular genetic features in a cohort of lipomatous SFTs. A hybrid-capture–based next-generation sequencing panel was employed to detect NAB2-STAT6 gene fusions at the RNA level. In addition, the RNA expression levels of 507 genes were evaluated using this panel, and were compared with a control cohort of nonlipomatous SFTs. Notably, 5 of 11 (45%) of lipomatous SFTs in the current series harbored the uncommon NAB2 exon 4–STAT6 exon 4 gene fusion variant, which is observed in only 0.9% to 1.4% of nonlipomatous SFTs. Furthermore, lipomatous SFTs displayed significant differences in gene expression compared with their nonlipomatous counterparts, including up-regulation of the gene peroxisome proliferator activated receptor-γ (PPARG). Peroxisome proliferator activated receptor-γ is a nuclear receptor regulating adipocyte differentiation, providing a possible explanation for the fat-forming component in lipomatous SFTs. In summary, the current study provides a possible molecular genetic basis for the distinct morphologic features of lipomatous SFTs.

Authors with CRIS profile

Florian Haller Professur für Diagnostische Molekularpathologie Fulvia Ferrazzi Department of Nephropathology Evgeny Moskalev Institute of Pathology Robert Grützmann Lehrstuhl für Allgemein- und Viszeralchirurgie Norbert Meidenbauer Department of Medicine 5 – Haematology and Oncology Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Berliner Institut für Gesundheitsforschung (BIH) DE Germany (DE) Leiden University Medical Center NL Netherlands (NL) Univerzita Karlova v Praze / Charles University in Prague CZ Czech Republic (CZ) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Universitätsklinikum Göttingen DE Germany (DE)

How to cite

APA:

Haller, F., Schlieben, L.D., Ferrazzi, F., Michal, M., Stöhr, R., Moskalev, E.,... Agaimy, A. (2021). Lipomatous Solitary Fibrous Tumors Harbor Rare NAB2-STAT6 Fusion Variants and Show Up-Regulation of the Gene PPARG, Encoding for a Regulator of Adipocyte Differentiation. American Journal of Pathology. https://dx.doi.org/10.1016/j.ajpath.2021.03.012

MLA:

Haller, Florian, et al. "Lipomatous Solitary Fibrous Tumors Harbor Rare NAB2-STAT6 Fusion Variants and Show Up-Regulation of the Gene PPARG, Encoding for a Regulator of Adipocyte Differentiation." American Journal of Pathology (2021).

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