Fusion of anETS-family gene,EIAF, toEWS by t(17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy

Kaneko, Yasuhiko; Yoshida, Kôichi; Handa, Masafumi; Toyoda, Yasunori; Nishihira, Hirokazu; Tanaka, Yukichi; Sasaki, Yoshiro; Ishida, Setsuko; Higashino, Fumihiro; Fujinaga, Kei

doi:10.1002/(sici)1098-2264(199602)15:2<115::aid-gcc6>3.0.co;2-6

Cited by 217 publications

(9 citation statements)

References 16 publications

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“…The ERG gene, located at 21q22, is the fusion partner to EWSR1 in about 5 to 10% of cases of Ewing sarcoma [4]. Other fusion partners described in the ETS family members include ETV1 (7p22) [5], ETV4 (17q12) [6], and FEV (2q33) genes [7]. These translocations result in the fusion of the N-terminal transactivation domain of EWSR1 with the C-terminal DNA-binding domain of the ETS family member generating a potent and oncogenic transcription factor [8].…”

Section: Introductionmentioning

confidence: 99%

Malignant round cell tumor of bone with EWSR1-NFATC2 gene fusion

et al. 2014

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Gene rearrangements involving the Ewing sarcoma breakpoint region 1 (EWSR1) gene are seen in a broad range of sarcomas and some nonmesenchymal neoplasms. Ewing sarcoma is molecularly defined by a fusion of the EWSR1 gene (or rarely the related FUS gene) to a member of the E26 transformation-specific (ETS) family of transcription factors, frequently the EWSR1-FLI1 fusion. More recently, EWSR1 gene fusion to non-ETS family members, including the nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 2 (NFATC2) gene, has been reported in a histological variant of Ewing sarcoma. Here, we report a malignant round cell tumor of bone with an EWSR1-NFATC2 fusion gene. This report builds upon the unusual morphological and clinical presentation of bone neoplasms containing an EWSR1-NFATC2 fusion gene.

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Section: Introductionmentioning

confidence: 99%

Malignant round cell tumor of bone with EWSR1-NFATC2 gene fusion

et al. 2014

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“…We have shown that EWS gene (other fusion partner) codes for an RNA binding protein which speci®cally binds to poly G and poly U (Ohno et al, 1994). Interestingly, this EWS gene is also fused with a variety of transcriptional factors which includes ATF-1, WT1, ER81/ETC1, CHOP and PEA3 in dierent solid tumors (Zucman et al, 1993b, Ladanyi andGerald, 1994;Gerald et al, 1995;Jeon et al, 1995;Panagopoulos et al, 1996;Kaneko et al, 1996;Clark et al, 1996). Therefore studying the functional aspects of EWS-fusion proteins (EWS-erg and EWS Fli-1) may provide a clue for the activation of EWS-fusion products in a wide spectrum of cancers.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias

et al. 1997

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Two ets family members, namely erg and Fli-1 are fused with two EWS family members namely EWS and TLS/FUS as a result of chromosome translocation in human solid tumors and leukemias. EWS-erg and EWS-Fli-1, which are involved in greater than 95% of Ewing family of tumors, were shown to function as transcriptional activators. TLS/FUS-erg, which is involved in human myeloid leukemias also functions as a transcriptional activator. Expression of these fusion proteins (EWS-erg and EWS-Fli-1) are shown to be essential for maintaining the oncogenic and tumorigenic properties of tumor cells. Cancer is thought to be caused not only by uncontrolled cell proliferation but also by deregulation of programmed cell death. Therefore, we have studied the role of normal (Fli-1 and erg) and aberrant fusion proteins (EWS-erg, EWS-Fli-1 and TLS/FUS-erg) in apoptosis. We have found that expression of normal (Fli-1 and erg) and aberrant fusion proteins inhibit the apoptosis of NIH3T3 cells induced by either serum deprivation or by treatment with calcium ionophore. We have also observed similar suppression of apoptosis in Ewing's sarcoma cells expressing EWS-Fli-1 and EWS-erg proteins suggesting that these fusion proteins may be responsible for the decreased ability of these tumor cells to undergo apoptosis. Inhibition of the expression of these aberrant fusion proteins by antisense RNA technique resulted in increased susceptibility to apoptosis leading to the death of tumor cells. Therefore, our results suggest that one can use therapeutic agents which can down regulate the expression of fusion proteins in combination with chemotherapeutic agents as an effective treatment for these human solid tumors and leukemias.

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“…In particular, the biological consequence is an upregulated expression of genes normally repressed by CIC, including polyoma enhancer activator 3 (PEA3) family members of ETS-related transcription factors ETV1, ETV4, and ETV5 [14,16,24,33]. Of note, PEA3 belongs to the family of ETS-related transcription factors reported as rare fusion partners of EWSR1 in ES [22,34,35].…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation Profiling for Diagnosing Undifferentiated Sarcoma with Capicua Transcriptional Receptor (CIC) Alterations

Miele

Vito

Ciolfi

et al. 2020

IJMS

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Undifferentiated soft tissue sarcomas are a group of diagnostically challenging tumors in the pediatric population. Molecular techniques are instrumental for the categorization and differential diagnosis of these tumors. A subgroup of recently identified soft tissue sarcomas with undifferentiated round cell morphology was characterized by Capicua transcriptional receptor (CIC) rearrangements. Recently, an array-based DNA methylation analysis of undifferentiated tumors with small blue round cell histology was shown to provide a highly robust and reproducible approach for precisely classifying this diagnostically challenging group of tumors. We describe the case of an undifferentiated sarcoma of the abdominal wall in a 12-year-old girl. The patient presented with a voluminous mass of the abdominal wall, and multiple micro-nodules in the right lung. The tumor was unclassifiable with current immunohistochemical and molecular approaches. However, DNA methylation profiling allowed us to classify this neoplasia as small blue round cell tumor with CIC alterations. The patient was treated with neoadjuvant chemotherapy followed by complete surgical resection and adjuvant chemotherapy. After 22 months, the patient is disease-free and in good clinical condition. To put our experience in context, we conducted a literature review, analyzing current knowledge and state-of-the-art diagnosis, prognosis, and clinical management of CIC rearranged sarcomas. Our findings further support the use of DNA methylation profiling as an important tool to improve diagnosis of non-Ewing small round cell tumors.

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Fusion of anETS-family gene,EIAF, toEWS by t(17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy

Cited by 217 publications

References 16 publications

Malignant round cell tumor of bone with EWSR1-NFATC2 gene fusion

Malignant round cell tumor of bone with EWSR1-NFATC2 gene fusion

Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias

DNA Methylation Profiling for Diagnosing Undifferentiated Sarcoma with Capicua Transcriptional Receptor (CIC) Alterations

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