Role of Next-Generation Sequencing as a Diagnostic Tool for the Evaluation of Bone and Soft-Tissue Tumors

Szurián, Kinga; Kashofer, Karl; Liegl‐Atzwanger, Bernadette

doi:10.1159/000478662

Cited by 24 publications

(21 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These studies revealed an EWSR1 gene rearrangement at 22q12 (Figure A). Subsequently, tissue was referred to another institution in an attempt to identify the partner gene via the Archer DX platform (ArcherDX Inc., Boulder, Colorado), utilizing massively parallel next‐generation RNA sequencing by synthesis using semiconductor technology on a Personal Genomics Machine (Ion Torrent/Thermo Fischer Scientific, Waltham, Massachusetts) . The results indicated an EWSR1‐PBX3 gene fusion in which exon 7 of EWSR1 (reference gene accession number NM_001163286) was fused in‐frame to exon 5 of PBX3 (reference gene accession number NM_001134778) (Figure B).…”

Section: Case Reportmentioning

confidence: 99%

EWSR1‐PBX3 gene fusion in cutaneous syncytial myoepithelioma

et al. 2019

View full text Add to dashboard Cite

Cutaneous syncytial myoepithelioma (CSM) is a recently recognized, histopathological variant of myoepithelial (ME) tumors of the skin. It is characterized by a syncytial arrangement of spindled, ovoid, and/or epithelioid cells forming a well-circumscribed, unencapsulated dermal nodule.There is a paucity of intervening stroma, and absent duct or gland formation. Strong immunohistochemical staining for S100 and epithelial membrane antigen (EMA) has been described, while cytokeratin expression has been uncommon. The majority of CSMs harbor a rearrangement involving the EWSR1 gene. Although various fusion partner genes have been discovered in ME tumors at other anatomic sites, none has yet been described in CSM. We present a case of CSM represented clinically by a papule on the mid-upper back of a healthy 44-year-old female. It exhibited morphological and immunohistochemical features of a CSM with strong, diffuse S100 and alpha-actin expression, and focal positivity for EMA and cytokeratin AE1/AE3. Fluorescence in-situ hybridization showed an EWSR1 gene rearrangement. Massively parallel next-generation RNA sequencing revealed PBX3 as the fusion partner. The EWSR1-PBX3 gene fusion has been previously identified in three cases of ME tumors of bone and soft tissue, and in a case of retroperitoneal leiomyoma. This is the first report of an EWSR1-PBX3 fusion in CSM.

show abstract

Section: Case Reportmentioning

confidence: 99%

EWSR1‐PBX3 gene fusion in cutaneous syncytial myoepithelioma

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Immunohistochemical analysis has played little role in the diagnosis of bone tumors, although recent molecular advances have provided pathologists with specific targets amenable to antibody interrogation in some tumors such as giant cell tumor of bone and chondroblastoma [17] . Polymerase chain reaction (PCR) [18][19][20] and, more recently, massively parallel next generation sequencing (NGS) based assays have provided additional tools for assessing molecular alterations in bone tumors [21][22][23] . However, it is worth noting that many of these ancillary testing modalities are exquisitely sensitive to conventional processing techniques, particularly decalcification, and care must be taken when processing bony lesions with consideration for downstream testing that may take place after the histopathological examination.…”

Section: Introductionmentioning

confidence: 99%

Genetic characteristics and molecular diagnostics of bone tumors

Suster¹,

Suster²

2021

JCMT

View full text Add to dashboard Cite

The diagnosis of primary tumors of bone relies heavily on clinicopathological and radiological correlation and is often best performed in a multidisciplinary setting. Bone tumors comprise a heterogenous category of human lesions ranging from benign to malignant neoplasms. These tumors affect a wide age range and can become problematic for diagnosis when less common entities are encountered. Traditionally the pathological diagnosis of many bone tumors has been based primarily on the evaluation of hematoxylin and eosin-stained glass slides, sometimes combined with ancillary diagnostic techniques such as immunohistochemistry, conventional cytogenetics, fluorescence in situ hybridization, and polymerase chain reaction-based assays. More recently, the advent of massively parallel sequencing-based techniques has opened new avenues for diagnostic testing in bone tumors; however, these new testing modalities are sensitive to traditional decalcification procedures that are commonly used in the routine processing of bony specimens. Herein we provide a focused review concentrating on the molecular genetic features of bone tumors with specific, recurrent genetic alterations that make them appealing targets for directed ancillary testing by conventional or molecular techniques. In addition, specimen handling with regards to decalcification procedures are discussed and the different types of testing modalities available are reviewed.

show abstract

“…Gene fusions are an important category of driver mutations in paediatric sarcomas [1]. While well-characterized and commonly occurring gene fusions can be identified by standard laboratory assays such as FISH and RT-PCR, an advanced technique such as next-generation sequencing (NGS) is often required to identify rare or novel gene fusions [2]. Gene fusion identification serves to confirm a pathological diagnosis, and is also important in relation to treatment as certain gene fusions have drug-targetable domains [3].…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we report clinical, pathological and molecular features of three unique epidural sarcomas presenting with neurological compromise located in the cranium and spine. We describe the use of a next-generation sequencing-based assay (Archer FusionPlex Sarcoma assay (ArcherDX, Inc)) as a technique to identify gene fusions in these three primary paediatric epidural sarcomas [2, 4, 5].…”

Section: Introductionmentioning

confidence: 99%

Primary paediatric epidural sarcomas: molecular exploration of three cases

et al. 2019

View full text Add to dashboard Cite

Background Primary paediatric epidural sarcomas are extremely rare. Overall, there remains a paucity of knowledge in paediatric epidural sarcomas owing to the infrequent number of cases. The Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) is a next-generation sequencing assay that has been reported to be a useful technique to detect recurrent fusion in sarcomas. We report the molecular exploration of 3 primary paediatric epidural sarcomas—one in the cranium (mesenchymal chondrosarcoma) and 2 in the spine (mesenchymal chondrosarcoma and Ewing sarcoma respectively). Case presentation This is a study approved by the hospital ethics board. Clinico-pathological information from 3 consenting patients with primary epidural sarcomas was collected. These selected tumours are interrogated via Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) for genomic aberrations. Results were validated with RT-PCR and Sanger sequencing. All findings are corroborated and discussed in concordance with current literature. Our findings show 2 variants of the HEY1-NCOA2 gene fusion: HEY1 (exon 4)-NCOA2 (exon 13) and HEY1 (exon 4)-NCOA2 (exon 14), in both mesenchymal chondrosarcoma patients. Next, the Ewing sarcoma tumour is found to have EWSR1 (exon 10)-FLI1 (exon 8) translocation based on NGS. This result is not detected via conventional fluorescence in situ testing. Conclusions This is a molecularly-centered study based on 3 unique primary paediatric epidural sarcomas. Our findings to add to the growing body of literature for these exceptionally rare and malignant neoplasms. The authors advocate global collaborative efforts and in-depth studies for targeted therapy to benefit affected children.

show abstract

Role of Next-Generation Sequencing as a Diagnostic Tool for the Evaluation of Bone and Soft-Tissue Tumors

Cited by 24 publications

References 95 publications

EWSR1‐PBX3 gene fusion in cutaneous syncytial myoepithelioma

EWSR1‐PBX3 gene fusion in cutaneous syncytial myoepithelioma

Genetic characteristics and molecular diagnostics of bone tumors

Primary paediatric epidural sarcomas: molecular exploration of three cases

Contact Info

Product

Resources

About