Pathogenesis of Ewing sarcoma: A review

Abstract

Ewing sarcoma is a rare sarcoma of bone and soft tissue that uncommonly involve the head and neck. It is the second most common malignant tumor seen in children and young adults. It is most common observed during the second or third decade, with a male predilection. In the head and neck region, it involves skull, clavicle, maxilla, and mandible. The reported incidence of this tumor is only 1-3 cases per million of population per year and skull tumors constitute about 2% of it. The cell of origin is still unclear as there are several literature supporting both the neural crest mesenchymal progenitor/stem cells hypothesis. Ewing sarcoma is believed to be derived from recurrent EWS/E-twenty six (ETS) oncogenic fusions, which result in altered gene expression in the cell and other mechanisms. This altered gene expression is followed by the abnormal regulation in the expression of several genes and non-coding RNAs. In Ewing sarcoma, the translocation of t(11;22)(q24;q12) is considered as the primary mechanism for tumorigenesis. The tumor is characterized by the rearrangement of EWS gene on chromosome 22q12 and the fusion partners from the ETS oncogene family, chimeric transcription factor, which is responsible for the Ewing sarcoma oncogenic program. A hybrid gene is formed by the fusion of EWSR1 in 22q12 with the FLI1 gene in 11q24. EWS/FLI is the common chimeric protein that is expressed in Ewing's sarcoma. The expression of this protein results in the growth arrest and cell death, when they are expressed in primary cell lines. The expression of these proteins in primitive cell or tumor cell causes differentiation defects resulting in oncogenesis. In this review, we have made an attempt to have an insight into the possible mechanism of pathogenesis and cell of origin of Ewing sarcoma.

Ewing Sarcoma in the Sciatic Nerve: Case Report

“…On immunohistochemistry, about 90% of ESFT cases are positive for CD99, a membrane glycoprotein product of the MIC2 gene. [5][6][7] There are hypotheses about the origin of these tumors, among them: the theory of parental mesenchymal stem cells, and that of an origin in a primitive nerve cell or in the postganglionic cholinergic neurons of the parasympathetic system; however, the true progenitor cell of these tumors remains unknown. 1,3,7 About 25% of cases of ESFT are in soft tissues, affecting patients between 10 and 30 years of age, with a peak incidence at 20 years of age.…”

“…[5][6][7] There are hypotheses about the origin of these tumors, among them: the theory of parental mesenchymal stem cells, and that of an origin in a primitive nerve cell or in the postganglionic cholinergic neurons of the parasympathetic system; however, the true progenitor cell of these tumors remains unknown. 1,3,7 About 25% of cases of ESFT are in soft tissues, affecting patients between 10 and 30 years of age, with a peak incidence at 20 years of age. The most frequent sites include the chest wall, the paravertebral musculature, the lower extremities, and the retroperitoneal space.…”

Molecular biology of sarcoma

“…There are several variants of these translocations. Expression of the fusion protein in normal cells leads to their death, while in an undifferentiated or malignant cells it causes disorders of differentiation resulting in the development of malignancy [56,57]. The effect of fusions between genes from the EWS and ETS families are new transcription factors that influence cellular processes related to proliferation, apoptosis, autophagy, and cell viability [17].…”

The Optimal Outcome of Suppressing Ewing Sarcoma Growth in vivo With Biocompatible Bioengineered miR-34a-5p Prodrug

“…MicroRNAs (miRNAs or miRs) are a superfamily of singlestranded noncoding RNAs (ncRNAs) consisting of [18][19][20][21][22][23][24][25] nucleotides that are derived from the genome (1)(2)(3). Through post-transcriptional regulation of target gene expression, miRNAs may control particular cellular pathways and play an important role in disease initiation, progression, and prognosis (4)(5)(6)(7)(8).…”

“…Other rare mutations include TP53, STAG2, and CDKN2A deletions (20,21). Moreover, ES is generally locally aggressive and has high metastatic potential, resulting in a 5year survival rate lower than 30% (22)(23)(24)(25). Currently, surgery, radiotherapy and chemotherapy have been introduced to offer effective remedy against ES.…”