Epithelioid Sarcoma: Opportunities for Biology-Driven Targeted Therapy

Noujaim, Jonathan; Thway, Khin; Bajwa, Zia; Bajwa, Ayeza; Maki, Robert G.; Jones, Robin L.; Keller, Charles

doi:10.3389/fonc.2015.00186

Cited by 42 publications

(45 citation statements)

References 117 publications

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“…In inoperable and metastatic cases, as in this case, the treatment remains largely palliative. In future, gene therapy targeting the genetic pathway in tumourigenesis of this aggressive neoplasm may provide a better prognosis in these patients …”

Section: Discussionmentioning

confidence: 99%

Proximal‐type epithelioid sarcoma of the vulva: Cytopathological diagnosis of a rare neoplasm

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Proximal‐type epithelioid sarcoma of the vulva: Cytopathological diagnosis of a rare neoplasm

et al. 2018

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“…MiR‐765 can also be a discriminator between MEC and ES when myoepithelial differentiation is questionable. In the future, using miRNAs in the diagnosis of ES to separate the three subgroups may help to determine whether they behave differently or not and also may possibly provide potential treatment options against functionally active miRNAs, as they were discussed by Noujaim (Noujaim et al, ).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic regulation of SMARCB1 By miR‐206, ‐381 and ‐671‐5p is evident in a variety of SMARCB1 immunonegative soft tissue sarcomas, while miR‐765 appears specific for epithelioid sarcoma. A miRNA study of 223 soft tissue sarcomas

Szepes

Papp

Szabó

et al. 2016

Genes Chromosomes & Cancer

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Complete/partial loss of SMARCB1 nuclear-immunopositivity is characteristic of a certain subset of soft tissue sarcomas (STSs). Our previous work showed that oncomiRs-206,-381, and 671-5p could silence the SMARCB1 mRNA and protein expression and that they display significant overexpression in epithelioid sarcomas (ESs). MiR-765 was overexpressed too, but functionally was inactive in the silencing. In the current work, using quantitative PCR, we conducted a miRNA study of 51 ESs, 20 rhabdoid tumors (RTs), 20 synovial sarcomas (SSs), 15 malignant peripheral nerve sheath tumors (MPNSTs), 11 myoepithelial carcinomas (MECs), and 10 extraskeletal myxoid chondrosarcomas (EMCSs) with complete/partial loss of SMARCB1 nuclear immunostain, in contrast to controls (SMARCB1-immunopositive) of 96 STSs, 13 melanomas and 10 sarcomatoid carcinomas. The SMARCB1 genetic status of ESs was determined by MLPA and FISH. A subset of ESs (5/51) showed biallelic deletion of SMARCB1 with no overexpression of any miRNA, suggesting these tumors could be the counterpart of pediatric RT, at least genetically. Another subset (5/51) was genetically either intact or monoallelic deleted with at least threefold overexpression of one of miR-206,-381,-671-5p, suggesting epigenetic regulation only. 39/51 ESs had a biallelic deletion (>20% by FISH and/or by MLPA) but with overexpressed miR-206,-381, and 671-5p, suggesting intratumoral heterogeneity, i.e., both genetic and epigenetic regulation. At least threefold overexpression of one of miR-206,-381, and 671-5p was detected in all MPNSTs, EMCSs, SSs and 7 MCs. Except for ESs, four SSs and one MPNST, there was no event above threefold overexpression of miR-765 among all 195 tested tumors. Our results suggest a general role of miR-206,-381, and 671-5p in SMARCB1 gene silencing of ES, MC, EMCS, MPNST and SS. In the future, miR-765 could possibly be a diagnostic tool for ES because of its 97% specificity and 80% sensitivity. © 2016 Wiley Periodicals, Inc.

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“…Epithelioid sarcoma is rare (less than 1% of all soft tissue sarcomas) and aggressive type of sarcoma occurring mainly in children and young adults. Although it is a tumour of mesenchymal origin, the cells have both mesenchymal and epithelial markers [48].…”

Section: Epithelioid Sarcomamentioning

confidence: 99%

Molecular biology of sarcoma

et al. 2019

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Soft tissue sarcomas are a large group of heterogenous neoplasms, many of them are highly aggressive. Most of the cases are sporadic, without any well-defined pathogenetic factor. Potential risk factors are ionizing radiation, lymphatic oedema (secondary angiosarcoma of the breast), viral infections (HHV8 and Kaposi sarcoma), exposure to chemical factors (vinyl chloride and hepatic angiosarcoma). Genetic susceptibility plays a role in a minority of cases. However, mutations in TP53, ATM and ATR genes are associated with enhanced susceptibility to radiation. Li-Fraumeni syndrome (autosomal dominant TP53 mutation) predisposes to development of malignancies, one third of them are sarcomas. Genetic alterations observed in sarcomas could be divided into three major groups characterized by: (1) chromosome translocations; (2) simple karyotype and mutations; (3) variably complex karyotypes. A large part of sarcomas belong to the first group and the specific chromosal translocations could be utilized in the diagnostic process. A smaller number of sarcomas could be assigned to the second group, e.g. desmoid fibromatosis (CTNNB1 or APC mutations) and GIST (KIT, PDGFRA, or less frequently BRAF, SDH, NF1). A large number of sarcomas are characterized by complex and variable karyotypes. Gene copy number alterations are frequent in this group, e.g. in well-differentiated liposarcoma there is an amplification of MDM2, CDK4 and HMGA2 genes or sarcoma-specific chromosomal break regions present in the CHOP gene in myxoid liposarcoma and FKHR in alveolar rhabdomyosarcoma.

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Epithelioid Sarcoma: Opportunities for Biology-Driven Targeted Therapy

Cited by 42 publications

References 117 publications

Proximal‐type epithelioid sarcoma of the vulva: Cytopathological diagnosis of a rare neoplasm

Proximal‐type epithelioid sarcoma of the vulva: Cytopathological diagnosis of a rare neoplasm

Epigenetic regulation of SMARCB1 By miR‐206, ‐381 and ‐671‐5p is evident in a variety of SMARCB1 immunonegative soft tissue sarcomas, while miR‐765 appears specific for epithelioid sarcoma. A miRNA study of 223 soft tissue sarcomas

Molecular biology of sarcoma

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