EWSR1-FLI1 fusion

In confirmation of the validity of this method, hierarchical clustering revealed the characteristic EWSR1-FLI1 fusion in Ewing sarcoma. Furthermore, assessing the effects of in silico edge perturbations and simulated gene knockouts as quantified by changes in curvature, we found non-trivial gene associations not previously identified.

No abstract available

Multi-focal LCH developing after Ewing sarcoma treatment has previously not been reported in the literature. Deep sequencing of both tumors showed biologically distinct mechanisms that led to development of Ewing sarcoma and subsequent multi-focal bone LCH. More studies need to be performed to understand if these distinct tumors are arising from common lineage progenitor cells or represent an unfortunate secondary primary tumor.

SSEA4-specific CAR T cells specifically interacted with SSEA4 positive EwS cells in a strictly antigen-dependent manner, resulting in effective tumor cell lysis in vitro. We conclude that targeting of SSEA4 with CAR T cells or alternative immune therapeutics could be an attractive strategy to eliminate tumor cell subsets with high propensity to drive disease progression in EwS and therefore deserves further evaluation towards clinical translation.

Our study shows that NGS could efficiently facilitate the definitive diagnosis of ES and its mimics. We also revealed a diverse immune-genomic landscape of these SRCS, indicative of potential therapeutic opportunities targeting HRD and immune check-point in specific subtypes of these sarcoma entities.

Also, despite its rarity, PCES should be included in the differential diagnosis of small, round, blue cell tumors at cutaneous sites. Our case also exemplifies common biases in medical decision-making, including premature closure and anchoring bias which can result in misdiagnosis or diagnostic delay and associated delay in appropriate management.

Primary superficial Ewing sarcoma is extremely rare, and this is only the second molecularly confirmed case of rectal origin. Further studies are needed to better understand the clinical behavior of rare rectal and superficial Ewing sarcomas compared with their more common bone and deep soft tissue counterparts.

Primary superficial Ewing sarcoma is extremely rare, and this is only the second molecularly confirmed case of rectal origin. Further studies are needed to better understand the clinical behavior of rare rectal and superficial Ewing sarcomas compared with their more common bone and deep soft tissue counterparts.

PRKCB IHC is sensitive (98%) and specific (96%) in detecting EWSR1 rearranged ES. PRKCB is a reliable antibody for diagnosing ES in routine practice.

Although the patient received multidisciplinary treatment including chemotherapy regimens of etoposide plus cisplatin; focal radiotherapy focusing on the cerebrum, lung, and kidneys; and a subsequent palliative gastrointestinal operation, he eventually died of multiple organ functional failure. This patient with APC gene amplification showed excellent sensitivity to radiotherapy for intrapulmonary and intracranial lesions, suggesting that APC gene amplification may be related to radiotherapy sensitivity. However, further clinical research is needed.

Using reconstituted microtubule (MT) polymerization in vitro and cell-based chemical probe competition assays, we demonstrate that TK216 acts as an MT destabilizing agent. This work defines the mechanism of cytotoxicity of TK216, explains the synergy observed with vincristine, and calls for a reexamination of ongoing clinical trials with TK216.

We screened the anti-tumor effects of 214 anti-cancer drugs in NCC-ES2-C1 cells and found that the drugs which effectively reduced the proliferation of NCC-ES2-C1 cells. We concluded that NCC-ES2-C1 cells are a useful resource to study functions of the EWSR1-FLI1 fusion gene, investigate phenotypic changes caused by genes and proteins, and evaluate the anti-tumor effects of novel drugs.

Finally, we further show that statins impair tumor growth in different Ewing PDX models. Altogether, the data show that statins, which are off-patent, well-tolerated, and inexpensive compounds, should be strongly considered in the therapeutic arsenal against this deadly childhood disease.

Currently, we are in a process of elucidating the molecular mechanism of EWSR1 knockdown dependent mitigation of mitotic arrest. Successful completion of the study may shed light on how/whether haploinsufficiency of EWSR1 contributes to the molecular pathogenesis of Ewing sarcoma.

CCK-8 assay demonstrated an increased chemoresistance for tumorspheres versus normal adherent culture especially for doxorubicin, which was confirmed by reduction in PARP cleavage...BLK knockdown reduced CSC-like properties including abrogation of tumorsphere formation and reduction in the levels of SOX2 and NANOG. Together, this work for the first time identifies a CSC-like population in DSRCT and BLK as a potential DSRCT CSC target.

Comprehensive genomic characterization of NCI PDMR models generated from rare cancers solves an unmet need in the community. It will serve as a valuable resource for translational researchers interested in pre-clinical drug development and discovery.

These results demonstrate that targeted RNA-seq is a valuable tool to detect fusions in FFPE samples of rare tumors such as CCOC and CCC. The results also confirm the observations that CCOC is driven by fusions between EWSR1 and CREB family transcription factors, including ATF1 and CREM. To our knowledge, this is the second report of CCOC with an EWSR1-CREM translocation.

Due to the rarity of these tumors, there are no standard therapeutic guidelines and treatment consists of surgery, various chemotherapy regimens and/or radiotherapy. In this article, we report the case of a 30-year-old female with peripheral-type PNET (pPNET) of the ovary featuring Ewing sarcoma breakpoint region 1-Friend leukemia integration 1 (EWSR1-FLI1) fusion transcript, confirmed by next-generation sequencing (NGS).

No abstract available

EWSR1-FLI1 fusion is not rare in m-PTC and it is associated with the acquisition of small-cell phenotype. The EWSR1 gene rearrangement is a frequent event in m-PTC and is related to the classical pattern of m-PTC.

Notably, a combination treatment of a selective HDAC6 and doxorubicin (a DNA damage agent used as a standard therapy of EWS patients) dramatically inhibits tumor growth in two EWS murine xenograft models. These results could lead to suitable and promising therapeutic alternatives for patients with EWS.

Molecular analysis revealed a EWSR1-FLI1 fusion transcript supporting the diagnosis of a primary extra-osseous ES of the thyroid. The patient received adjuvant chemotherapy and has no evidence of recurrent disease.

Down-modulation of cis-mediated EWSR1-FLI1 activity, observed in STAG2-LOF conditions, is associated with enhanced migration and invasion properties of Ewing cells previously observed in EWSR1-FLI1 cells. Our study illuminates a process whereby STAG2-LOF fine-tunes the activity of an oncogenic transcription factor through altered CTCF-anchored loop extrusion and cis-mediated enhancer mechanisms.

Genomic sequencing of refractory/relapsed sarcomas showed a low mutation burden. RNA analysis resulted in identification of potential novel therapeutic targets. Further analysis of patient molecular subgroups and therapeutic strategies is ongoing.

Surgical treatment and radiotherapy have their pros and cons, which may give rise to different treatment strategies in different centers around the world. This review article discusses some of these controversies and reproduces the highlights from recent publications with regard to diagnostics, systemic treatment, and surgical treatment of Ewing sarcoma.

Also of clinical relevance, of two mesothelioma models available, one carries an NF2 driver mutation and the other BAP1 and LATS2 and a PDX model for Hurthle cell carcinoma has wide-spread loss of heterozygosity (LOH 80%). Models for other rare cancers are in development, including four cholangiocarcinoma PDXs with histopathologic confirmation that are currently being expanded for molecular characterization and distribution.

Neither the time of the cross-contamination event with IMR-32 is known nor was the final classification as a model for EFTs available with an associated STR profile. After a long road of errors and confusion, authentic CHP-100 is now characterized as a type II EWSR1-FLI1 fusion model 44?years after its establishment.

The child underwent EES therapy with good initial response, but had a subcutaneous relapse at 22 months. In addition to typical genetic alterations, Ewing sarcoma can also express CD7 and TCR/Ig rearrangement, which are not limited to lymphoma.

EWSR1 translocation can also be seen in anaplastic myoepithelial carcinoma but EWSR1-FLI1 fusion is specific to EFT and is present in 85% of cases. Conclusion This report raises awareness of sinonasal EFT, a rare entity which has a wide differential diagnosis, and demonstrates the use of molecular analysis as an adjunct to traditional histology, histochemistry and IHC to reach a definitive diagnosis.