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Hybrid schwannoma-perineurioma frequently harbors VGLL3 rearrangement.

ABSTRACT: Benign peripheral nerve tumors include schwannoma, neurofibroma, and perineurioma, as well as a recently recognized group of tumors with dual patterns of differentiation. The molecular pathogenesis of these so-called "hybrid" tumors remains poorly understood. Following identification of a novel CHD7-VGLL3 fusion gene in a hybrid schwannoma-perineurioma, we evaluated an expanded cohort of this tumor-type-as well as tumors with VGLL3 rearrangement identified from a curated molecular database-to characterize the prevalence of fusion genes among these tumors. Eighteen tumors met the inclusion criteria for this study. RNA sequencing identified VGLL3 rearrangement in 14 of these cases; the partner genes included CHD7 (ten cases), CHD9 (two cases), and MAMLD1 (two cases). Two cases possessed altogether unrelated fusions, including: DST-BRAF and SQSTM1-CDX1 fusion genes. Finally, two cases lacked identifiable fusion products. These findings highlight the molecular diversity of these neoplasms, with frequent rearrangement of VGLL3. More importantly, despite their dual pattern of differentiation, our results reveal the pathogenesis of hybrid schwannoma-perineurioma is unrelated to conventional schwannoma and perineurioma, thereby implying this tumor represents an altogether pathologically distinct entity.

SUBMITTER: Dickson BC

PROVIDER: S-EPMC8154639 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Hybrid schwannoma-perineurioma frequently harbors VGLL3 rearrangement.

Dickson Brendan C BC Antonescu Cristina R CR Demicco Elizabeth G EG Leong Dr Iona DI Anderson Nathaniel D ND Swanson David D Zhang Lei L Fletcher Christopher D M CDM Hornick Jason L JL

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20210301 6

Benign peripheral nerve tumors include schwannoma, neurofibroma, and perineurioma, as well as a recently recognized group of tumors with dual patterns of differentiation. The molecular pathogenesis of these so-called "hybrid" tumors remains poorly understood. Following identification of a novel CHD7-VGLL3 fusion gene in a hybrid schwannoma-perineurioma, we evaluated an expanded cohort of this tumor-type-as well as tumors with VGLL3 rearrangement identified from a curated molecular database-to ch ...[more]

PMID: 33649458

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Project description:UnlabelledHybrid isolates of Shiga toxin-producing Escherichia coli (STEC) and enterotoxigenic E. coli (ETEC) encoding heat-stable enterotoxin (ST) are being reported with increasing frequency from a variety of sources. However, information regarding the plasmids that these strains harbor is scarce. In this study, we sequence and characterize a plasmid, p7v, from the STEC/ETEC hybrid strain 7v. Whole-genome phylogenetic analyses of STEC/ETEC hybrid strains and prototype E. coli isolates of other pathotypes placed 7v in the Escherichia sp. cryptic lineage 1 (CL1) clade. The complete plasmid, p7v, was determined to be 229,275 bp and encodes putative virulence factors that are typically carried on STEC plasmids as well as those often carried on ETEC plasmids, indicating that the hybrid nature of the strain extends beyond merely encoding the two toxins. Plasmid p7v carries two copies of sta with identical sequences, which were discovered to be divergent from the sta sequences found in the prototype human ETEC strains. Using a nomenclature scheme based on a phylogeny constructed from sta and stb sequences, the sta encoded on p7v is designated STa4. In silico analysis determined that p7v also encodes the K88 fimbria, a colonization factor usually associated with porcine ETEC plasmids. The p7v sequence and the presence of plasmid-encoded virulence factors are compared to those of other STEC/ETEC CL1 hybrid genomes and reveal gene acquisition/loss at the strain level. In addition, the interrogation of 24 STEC/ETEC hybrid genomes for identification of plasmid replicons, colonization factors, Stx and ST subtypes, and other plasmid-encoded virulence genes highlights the diversity of these hybrid strains.ImportanceHybrid Shiga toxin-producing Escherichia coli/enterotoxigenic Escherichia coli (STEC/ETEC) strains, which have been isolated from environmental, animal, and human clinical samples, may represent an emerging threat as food-borne pathogens. Characterization of these strains is important for assessing virulence potential, aiding in the development of pathogen detection methods, and understanding how the hybrid strains evolve to potentially have a greater impact on public health. This study represents, to our knowledge, both the first characterization of a closed plasmid sequence from a STEC/ETEC hybrid strain and the most comprehensive phylogenetic analysis of available STEC/ETEC hybrid genomes to date. The results demonstrate how the mobility of plasmid-associated virulence genes has resulted in the creation of a diverse plasmid repertoire within the STEC/ETEC hybrid strains.

Project description:BackgroundAs a new entity included in the 4th edition of the WHO classification of tumours of soft tissue and bone in 2013, hybrid peripheral nerve sheath tumours are benign composite neoplasms that demonstrate features of more than one type of nerve sheath tumour, with a wide age distribution and a predilection for superficial location. Those involving deep sites are relatively rare. To the best of our knowledge, only one case of primary intraosseous hybrid peripheral nerve sheath tumours has been documented. In this article, we report another case of hybrid peripheral nerve sheath tumours occurring in bone with different clinical, radiological and pathological features from those in the previously reported cases.Case presentationA 28-year-old female presented with a painful nodule in the right tibia. Radiological examination revealed an oval eccentric osteolytic lesion in the proximal tibia. Histologically, the circumscribed but unencapsulated lesion demonstrated biphasic cellular differentiation. Bland, small epithelioid cells arranged in clusters in the myxoid or collagenous stroma and inconspicuous spindle cells scattered in the hypercellular areas were suggested to originate from Schwann cells according to the detection of S100. Both the elongated spindle cells with thin, wavy nuclei and the spindle cells in fascicular or storiform pattern in hypercellular areas showed a positive immunoreaction for epithelial membrane antigen, indicating perineurial differentiation. Based on histological and immunochemical examinations, the patient was diagnosed with hybrid epithelioid schwannoma/perineurioma. The lesion was resected and has not recurred for 8 months since resection.ConclusionThe present case is the second primary intraosseous hybrid peripheral nerve sheath tumour to be reported. This is also the first reported intraosseous tumour composed of epithelioid schwannoma and perineurioma with hypercellularity, indicating diverse involvement sites and a wide range of histological features among hybrid peripheral nerve sheath tumours. Awareness of such diversity is critical for accurate diagnoses. The morphological overlap with other spindle and epithelioid cell neoplasms, especially pure peripheral nerve sheath tumours, requires that immunochemical and molecular examinations be used as objective tools to provide the necessary information for a differential diagnosis.

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Hybrid schwannoma-perineurioma frequently harbors VGLL3 rearrangement.

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Hybrid schwannoma-perineurioma frequently harbors VGLL3 rearrangement.

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