title: Solitary fibrous tumors/hemangiopericytomas with different variants of the NAB2-STAT6 gene fusion are characterized by specific histomorphology and distinct clinicopathological features.
abstract: Recurrent somatic fusions of the two genes, NGFI-A-binding protein 2 (NAB2) and STAT6, located at chromosomal region 12q13, have been recently identified to be presumable tumor-initiating events in solitary fibrous tumors (SFT). Herein, we evaluated a cohort of 52 SFTs/hemangiopericytomas (HPCs) by whole-exome sequencing (one case) and multiplex RT-PCR (all 52 cases), and identified 12 different NAB2-STAT6 fusion variants in 48 cases (92%). All 52 cases showed strong and diffuse nuclear positivity for STAT6 by IHC. We categorized the fusion variants according to their potential functional effects within the predicted fusion protein and found strong correlations with relevant clinicopathological features. Tumors with the most common fusion variant, NAB2ex4-STAT6ex2/3, corresponded to classic pleuropulmonary SFTs with diffuse fibrosis and mostly benign behavior and occurred in older patients (median age, 69 years). In contrast, tumors with the second most common fusion variant, NAB2ex6-STAT6ex16/17, were found in much younger patients (median age, 47 years) and represented typical HPCs from deep soft tissue with a more aggressive phenotype and clinical behavior. In summary, these molecular genetic findings support the concept that classic pleuropulmonary SFT and deep-seated HPC are separate entities that share common features but correlate to different clinical outcome.
authors: Institute of Pathology, University Hospital Erlangen, Erlangen, Germany.
authors: Sarah
authors: S
authors: Barthelmeß
authors: Institute of Pathology, St. Vincent's Hospital, Karlsruhe, Germany.
authors: Helene
authors: H
authors: Geddert
authors: Institute of Pathology, SRH-Klinikum, Gera, Germany.
authors: Carsten
authors: C
authors: Boltze
authors: Institute of Pathology, University Hospital Erlangen, Erlangen, Germany.
authors: Evgeny A
authors: EA
authors: Moskalev
authors: Division of Theoretical Bioinformatics, German Cancer Research Center, Heidelberg, Germany.
authors: Matthias
authors: M
authors: Bieg
authors: Department of Thoracic Surgery, University Hospital Erlangen, Erlangen, Germany.
authors: Horia
authors: H
authors: Sirbu
authors: Division of Theoretical Bioinformatics, German Cancer Research Center, Heidelberg, Germany.
authors: Benedikt
authors: B
authors: Brors
authors: Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany; Genomics and Proteomics Core Facility, German Cancer Research Center, Heidelberg, Germany.
authors: Stefan
authors: S
authors: Wiemann
authors: Institute of Pathology, University Hospital Erlangen, Erlangen, Germany.
authors: Arndt
authors: A
authors: Hartmann
authors: Institute of Pathology, University Hospital Erlangen, Erlangen, Germany.
authors: Abbas
authors: A
authors: Agaimy
authors: Institute of Pathology, University Hospital Erlangen, Erlangen, Germany. Electronic address: florian.haller@uk-erlangen.de.
authors: Florian
authors: F
authors: Haller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D050939:Gene Fusion; D014644:Genetic Variation; D006393:Hemangiopericytoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D050800:STAT6 Transcription Factor / Q000235:genetics*; D054364:Solitary Fibrous Tumors / Q000235:genetics* / Q000473:pathology*
chemical_list: C491000:NAB2 protein, human; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human