scholarly journals FOXO1 gene involvement in a non-rhabdomyosarcomatous neoplasm

2021 ◽  
Author(s):  
Simon Haefliger ◽  
Muriel Genevay ◽  
Michel Bihl ◽  
Romina Marone ◽  
Daniel Baumhoer ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Soft Tissue ◽  
Genetic Heterogeneity ◽  
Gene Fusion ◽  
Fusion Gene ◽  
Soft Tissue Tumors ◽  
Gene Fusions ◽  
Mesenchymal Tumors ◽  
Myoepithelial Differentiation ◽  
Foxo1 Gene

AbstractMyoepithelial neoplasms of soft tissue are rare tumors with clinical, morphological, immunohistochemical, and genetic heterogeneity. The morphological spectrum of these tumors is broad, and the diagnosis often requires immunostaining to confirm myoepithelial differentiation. Rarely, tumors show a morphology that is typical for myoepithelial neoplasms, while the immunophenotype fails to confirm myoepithelial differentiation. For such lesions, the term “myoepithelioma-like” tumor was introduced. Recently, two cases of myoepithelioma-like tumors of the hands and one case of the foot were described with previously never reported OGT-FOXO gene fusions. Here, we report a 50-year-old woman, with a myoepithelial-like tumor localized in the soft tissue of the forearm and carrying a OGT-FOXO1 fusion gene. Our findings extend the spectrum of mesenchymal tumors involving members of the FOXO family of transcription factors and point to the existence of a family of soft tissue tumors that carry the gene fusion of the OGT-FOXO family.

scholarly journals Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors

Science ◽  
2018 ◽  
Vol 361 (6405) ◽  
pp. eaam8419 ◽  
Author(s):  
Nathaniel D. Anderson ◽  
Richard de Borja ◽  
Matthew D. Young ◽  
Fabio Fuligni ◽  
Andrej Rosic ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Ewing Sarcoma ◽  
Rna Binding ◽  
Fusion Gene ◽  
Soft Tissue Tumors ◽  
Gene Fusions ◽  
Gene Encoding ◽  
Reciprocal Translocations ◽  
Whole Genomes ◽  
Genomic Regions

Sarcomas are cancers of the bone and soft tissue often defined by gene fusions. Ewing sarcoma involves fusions between EWSR1, a gene encoding an RNA binding protein, and E26 transformation-specific (ETS) transcription factors. We explored how and when EWSR1-ETS fusions arise by studying the whole genomes of Ewing sarcomas. In 52 of 124 (42%) of tumors, the fusion gene arises by a sudden burst of complex, loop-like rearrangements, a process called chromoplexy, rather than by simple reciprocal translocations. These loops always contained the disease-defining fusion at the center, but they disrupted multiple additional genes. The loops occurred preferentially in early replicating and transcriptionally active genomic regions. Similar loops forming canonical fusions were found in three other sarcoma types. Chromoplexy-generated fusions appear to be associated with an aggressive form of Ewing sarcoma. These loops arise early, giving rise to both primary and relapse Ewing sarcoma tumors, which can continue to evolve in parallel.

scholarly journals Case Reports in Oncological Medicine Myoepithelioma: A New Rearrangement Involving the LPP Locus in a Case of Multiple Bone and Soft Tissue Lesions

2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Géraldine Pairet ◽  
Gaëlle Tilman ◽  
Rafaël Sciot ◽  
Thomas Schubert ◽  
Vasiliki Perlepe ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Protein Expression ◽  
Case Reports ◽  
S100 Protein ◽  
Soft Tissue Tumors ◽  
Molecular Karyotyping ◽  
Genomic Alteration ◽  
Navicular Bone ◽  
Mesenchymal Tumors ◽  
Epithelial Markers

We report a case of multiple myoepithelioma with synchronous bone and soft tissue tumors, associated with a new genomic alteration of the LPP locus. The lesions occurred in the foot by presenting one lump in the plantar soft tissue, and three lesions were detected in the calcaneus and in the navicular bone. All tumors showed the double immunophenotype of epithelial markers and S100 protein expression. No rearrangement of the EWSR1 and FUS loci was detected as reported in myoepitheliomas. However, molecular karyotyping detected an unbalanced rearrangement of the LPP locus, not involving the HMGA2 locus, which is the most frequent translocation partner observed in benign mesenchymal tumors such as lipomas (of soft tissue as well as parosteal) and pulmonary chondroid hamartoma.

Peripheral primitive neuroectodermal tumors in adults: documentation by molecular analysis.

1998 ◽  
Vol 16 (3) ◽  
pp. 1150-1157 ◽  
Author(s):  
E R Lawlor ◽  
J A Mathers ◽  
T Bainbridge ◽  
D E Horsman ◽  
A Kawai ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Molecular Analysis ◽  
Fusion Gene ◽  
Molecular Diagnostic ◽  
Gene Fusions ◽  
Primitive Neuroectodermal Tumors ◽  
Pathologic Features ◽  
Neuroectodermal Tumors ◽  
Objective Evidence ◽  
Peripheral Primitive Neuroectodermal Tumors

PURPOSE The Ewing tumor (ET) family of peripheral primitive neuroectodermal tumors (pPNETs) are primitive small round-cell tumors (SRCTs) of the bone and soft tissue that occur predominantly in children and adolescents. However, pPNETs only rarely enter the differential diagnosis of bone and soft tissue SRCTs in adults. Recently, gene fusions between the EWS gene and different members of the ETS transcription factor family have been shown to occur in virtually all pPNETs and thus constitute a pathognomonic marker for this tumor subclass. The aim of the present study was to document EWS/ETS fusion gene expression in suspected pPNETs of adults as objective evidence for the existence of this tumor family in older patients. PATIENTS AND METHODS The three contributing molecular diagnostic laboratories retrospectively compiled a cohort of all SRCT cases in which EWS/ETS gene fusions had been shown by molecular analysis. This cohort was surveyed for cases that occurred in patients aged 40 years or older, which were then analyzed for their clinical and pathologic features. RESULTS Nine patients between 40 and 65 years of age were found to have tumors positive for EWS/ETS gene fusions. Standard histopathologic and clinical features of these cases, other than age, were similar to those of childhood pPNETs. Patients were initiated on appropriate therapy after molecular analysis confirmed the diagnosis of pPNET. CONCLUSION Identification of an EWS/ETS gene fusion is useful in providing objective evidence of the diagnosis of pPNET in patients over the age of 40 years. This diagnosis should be considered in adults who present with bone and soft tissue SRCTs and appropriate biopsy specimens should be collected for molecular analysis at the time of diagnosis.

scholarly journals PATH-24. DETECTION OF POINT MUTATIONS AND GENE FUSIONS FROM CIRCULATING CELL-FREE DNA (CFDNA) OF GLIOBLASTOMA (GBM) PATIENTS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii169-ii169
Author(s):  
Milana Frenkel-Morgenstern ◽  
Vikrant Palande ◽  
Rajesh Detroja ◽  
Alessandro Gorohovski ◽  
Rainer Glass ◽  
...  
Keyword(s):  
Drug Targets ◽  
Gene Fusion ◽  
Fusion Gene ◽  
Point Mutations ◽  
Invasive Procedure ◽  
Clonal Diversity ◽  
Healthy Controls ◽  
Gene Fusions ◽  
Non Invasive ◽  
Tumor Dna

Abstract BACKGROUND GBM is characterized by intratumoral heterogeneity. Tumor heterogeneity, clonal diversity and mutation acquisition hamper the ability to tailor personalized therapy for GBM. Tumor sampling has limited ability to accurately capture the molecular landscape of the tumor and to disclose acquired molecular aberrations. Mutation analysis of cfDNA is a non-invasive procedure which may overcome these limitations as it may reflect the real composition of the tumor and track the molecular evolution. We sequenced cfDNA of GBM patients and assessed mutation patterns and fusion genes. METHODS We collected blood and respective tumor samples from 27 GBM patients and blood samples from 14 healthy controls. Tumor DNA, cfDNA and WBC DNA were sequenced using deep sequencing procedures. The data were analyzed for detection of single nucleotide polymorphism (SNPs) and gene-gene fusions. RESULTS GBM cfDNA concentrations were significantly elevated (median: 23.63 ng/mL; range 12.6–137) compared to healthy controls (median 2.06; range 1.68–7.62) (p < 0.0001). We identified unique SNPs in each glioma patient’s cfDNA and the corresponding tumor DNA including the top-10 most frequently mutated genes in GBM. For example, mutation of TP53 was detected in18.75%; EGFR in 37.5%; NF1-12.5%; LRP1B-25% and IRS4 in 25%. For gene-gene fusion we used the in-house fusion gene database, ChiTaRS 5.0, and identified fusions in cfDNA and tumor DNA. Thus, KMT2A-FLNA was the most frequent fusion found in 16.4% of samples. BCR-ABL1 in 8.82% and FGFR1-BCR in 2.94%. Other fusions included COL1A1-PDGFB (5.88%), NIN-PDGFRB (5.88%), KIF5B-RET (5.88%) and also TPM3-ROS1(2.94%), TFG-ALK(2.94%), MSN-ALK (2.94%) and NPM1-ALK (2.94%) which may be targeted by brain penetrating drugs that are ROS1 and ALK inhibitors. CONCLUSIONS Our study suggests that plasma cfDNA analysis may help to uncover real time mutational and gene fusion status of GBM by a non-invasive procedure. It may identify drug targets based on personalized gene-gene fusions.

Infantile NTRK-associated Mesenchymal Tumors

2017 ◽  
Vol 21 (1) ◽  
pp. 68-78 ◽  
Author(s):  
Jessica L Davis ◽  
Christina M Lockwood ◽  
Catherine M Albert ◽  
Karen Tsuchiya ◽  
Douglas S Hawkins ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Molecular Mechanisms ◽  
Lung Metastases ◽  
Smooth Muscle Actin ◽  
Radical Resection ◽  
Soft Tissue Tumors ◽  
Mesenchymal Tumors ◽  
Variable Expression ◽  
Infantile Fibrosarcoma ◽  
Common Group

Pediatric fibroblastic/myofibroblastic lesions are a relatively common group of tumors with varying morphologies, for which the molecular mechanisms are becoming increasingly well characterized. Congenital infantile fibrosarcoma (CIFS), perhaps the most well studied of these lesions is characterized by a recurrent ETV6-NTRK3 gene fusion. However, a notable subset of locally aggressive congenital/infantile soft tissue lesions with similar morphologic features to CIFS, have not to-date, shown evidence of any canonical molecular aberration. We describe 6 patients with mesenchymal tumors composed of infiltrative fibroblastic/myofibroblastic tumor cells and showing a morphologic spectrum of features much analogous to that previously described in CIFS but without ETV6 fusion transcripts. These tumors lacked a uniform immunoprofile, but showed variable expression of CD34, S100, smooth muscle actin, and CD30. All patients first developed a mass in infancy (≤2 months of age). Using next-generation DNA sequencing, TMP3-NTRK1 fusions were identified in 4 cases, an LMNA-NTRK1 fusion in one case, and a variant EML4-NTRK3 fusion in one case. Similar to infantile fibrosarcoma, these tumors were locally aggressive (with local recurrences if incompletely excised) and rarely metastasized (lung metastases in one patient). Proper identification of these tumors including investigation for NTRK family gene rearrangements is essential for diagnostic accuracy, as well as for clinical management decisions. Given the morbidity associated with radical resection of large soft tissue tumors, children with unresectable, recurrent, and/or metastatic disease may benefit from treatment with NTRK targeted therapies.

scholarly journals Novel RGAG1-BCOR gene fusion revealed in a somatic soft tissue sarcoma with a long follow-up

2021 ◽  
Author(s):  
Mauro Vasella ◽  
Ulrich Wagner ◽  
Christine Fritz ◽  
Kati Seidl ◽  
Luca Giudici ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Gene Fusion ◽  
Soft Tissue Mass ◽  
Soft Tissue Tumors ◽  
Rt Pcr ◽  
Tissue Mass ◽  
Myxoid Chondrosarcoma ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

AbstractBCOR-rearranged sarcomas are rare and belong to the Ewing-like sarcomas (ELS). Their morphology and histopathological features make the diagnosis challenging. We present a case, initially diagnosed as an unusual extraskeletal myxoid chondrosarcoma (EMC). A 54-year-old male patient developed an asymptomatic swelling of the lower leg. Imaging showed a 9.5-cm large intramuscular soft tissue mass. Due to its morphological and immunohistochemical profile on biopsy, it was initially diagnosed as an EMC. The patient was treated by complete resection and adjuvant radiotherapy and remained free of tumor at 7 years follow-up. Using next-generation sequencing (NGS), we retrospectively identified RGAG1-BCOR gene fusion (confirmed by RT-PCR), which has not been described in somatic soft tissue tumors so far. This finding broadens the spectrum of partner genes in the BCOR-rearranged sarcomas in a tumor with a well-documented, long clinical follow-up.

scholarly journals Immunohistochemical Markers of Soft Tissue Tumors: Pathologic Diagnosis, Genetic Contributions, and Therapeutic Options

2015 ◽  
Vol 10s1 ◽  
pp. ACI.S32730 ◽  
Author(s):  
David M. Parham
Keyword(s):  
Soft Tissue ◽  
Fusion Gene ◽  
Anticancer Therapy ◽  
Soft Tissue Tumors ◽  
Gene Products ◽  
Ki 67 ◽  
New Techniques ◽  
Immunohistochemical Markers ◽  
Genetic Contributions ◽  
Cell Phenotypes

After ~30 years of widespread usage, immunohistochemistry (IHC) has become a standard method of diagnosis for surgical pathology. Because of the plethora of diagnoses and often subtle nature of diagnostic criteria, IHC finds particular utility in soft tissue tumors. The use of progressively small amounts of tissue for diagnosis highlights the importance of this method. The sensitivity and crispness of IHC stains have progressively improved with the advent of new techniques. Traditionally, IHC detects cell-typic markers that characterize cell phenotypes, such as chromogranin for neuroectodermal tissue, myogenin for skeletal muscle, and cytokeratin for epithelium. However, the advent of genetic discoveries have led to IHC testing for detection of fusion gene products or overexpressed oncogenes associated with deletions and mutations. Proliferation-based markers such as Ki-67 can also be used for prognosis and grading, but more standardization is needed. Development of monoclonal antibody-based pharmaceuticals, such as imatinib or crizotinib, holds the promise of tailored anticancer therapy. IHC thus has assumed importance not only for diagnosis but also for guidance of personalized medicine.

scholarly journals The Rapidly Expanding Group of RB1-Deleted Soft Tissue Tumors: An Updated Review

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 430
Author(s):  
Sasha Libbrecht ◽  
Jo Van Dorpe ◽  
David Creytens
Keyword(s):  
Soft Tissue ◽  
Spindle Cell ◽  
Adult Population ◽  
Suppressor Gene ◽  
Soft Tissue Tumors ◽  
Mesenchymal Tumors ◽  
Pleomorphic Liposarcoma ◽  
Molecular Features ◽  
Pleomorphic Lipoma ◽  
Older Adult Population

The classification of soft tissue tumors has evolved considerably in the last decade, largely due to advances in understanding the pathogenetic basis of many of these, sometimes rare, tumors. Deletion of Retinoblastoma 1 (RB1), a well-known tumor suppressor gene, has been implicated in the tumorigenesis of a particular group of soft tissue neoplasms. This group of so-called ”RB1-deleted soft tissue tumors” has been rapidly expanding in recent years, currently consisting of spindle cell/pleomorphic lipoma, atypical spindle cell/pleomorphic lipomatous tumor, pleomorphic liposarcoma, myofibroblastoma, cellular angiofibroma, and acral fibromyxoma. Most of these neoplasms, except pleomorphic liposarcoma, are considered benign entities and are mainly described in the older adult population. This article will review the currently known morphological, immunohistochemical, and molecular features of this heterogeneous group of mesenchymal tumors with an emphasis on differential diagnosis.

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