A novel EWS-WT1 gene fusion product in desmoplastic small round cell tumor is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene

Haim Werner; Gila Idelman; Moran Rubinstein; Patrick Pattee; Srinivasa R. Nagalla; Charles T. Roberts

doi:10.1016/j.canlet.2006.03.027

A novel EWS-WT1 gene fusion product in desmoplastic small round cell tumor is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene

Haim Werner^*, Gila Idelman, Moran Rubinstein, Patrick Pattee, Srinivasa R. Nagalla, Charles T. Roberts

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

Desmoplastic small round cell tumor (DSRCT) is a primitive sarcoma characterized by a recurrent chromosomal translocation, t(11;22)(p13;q12), which fuses the 5′ exons of the EWS gene to the 3′ exons of the WT1 gene. EWS-WT1 chimeras are heterogeneous as a result of fusions of different regions of the EWS gene to the WT1 gene. We report here a rare and novel EWS-WT1 variant, EWS-WT1 5/10, in a 6-year-old boy diagnosed with DSRCT and analyze the potential transactivation effect of the fusion oncoprotein. The predicted product is comprised of the N-terminal transactivation domain of EWS and lacks any sequence derived from the WT1 gene product. Nonetheless, the truncated protein was able to stimulate expression of the insulin-like growth factor-I receptor gene, a potent antiapoptotic receptor tyrosine kinase with potentially important roles in DSRCT etiology. These findings raise the possibility that the oncogenic potential of EWS-WT1 fusions is not necessarily a consequence of the fusion protein product per se.

Original language	English
Pages (from-to)	84-90
Number of pages	7
Journal	Cancer Letters
Volume	247
Issue number	1-2
DOIs	https://doi.org/10.1016/j.canlet.2006.03.027
State	Published - 8 Mar 2007

Funding

Funders	Funder number
FIRCA
National Institutes of Health
Fogarty International Center
National Institute of Diabetes and Digestive and Kidney Diseases
United States-Israel Binational Science Foundation
Israel Cancer Association

Keywords

DSRCT
EWS-WT1
IGF receptor
Insulin-like growth factor-I

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2006.03.027

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@article{535a5c5647a04cc88f070fd73ef2691e,

title = "A novel EWS-WT1 gene fusion product in desmoplastic small round cell tumor is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene",

abstract = "Desmoplastic small round cell tumor (DSRCT) is a primitive sarcoma characterized by a recurrent chromosomal translocation, t(11;22)(p13;q12), which fuses the 5′ exons of the EWS gene to the 3′ exons of the WT1 gene. EWS-WT1 chimeras are heterogeneous as a result of fusions of different regions of the EWS gene to the WT1 gene. We report here a rare and novel EWS-WT1 variant, EWS-WT1 5/10, in a 6-year-old boy diagnosed with DSRCT and analyze the potential transactivation effect of the fusion oncoprotein. The predicted product is comprised of the N-terminal transactivation domain of EWS and lacks any sequence derived from the WT1 gene product. Nonetheless, the truncated protein was able to stimulate expression of the insulin-like growth factor-I receptor gene, a potent antiapoptotic receptor tyrosine kinase with potentially important roles in DSRCT etiology. These findings raise the possibility that the oncogenic potential of EWS-WT1 fusions is not necessarily a consequence of the fusion protein product per se.",

keywords = "DSRCT, EWS-WT1, IGF receptor, Insulin-like growth factor-I",

author = "Haim Werner and Gila Idelman and Moran Rubinstein and Patrick Pattee and Nagalla, {Srinivasa R.} and Roberts, {Charles T.}",

note = "Funding Information: These studies were supported by grants from the Israel Cancer Association to H.W., the US-Israel Binational Science Foundation (BSF) and the Fogarty International Center (FIRCA) to H.W. and C.T.R., Jr, and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, to C.T.R., Jr. S.R.N. and C.T.R., Jr., thank T.B. Moore, M.D., for referral of this patient and Scott Kuhn for expert technical assistance.",

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doi = "10.1016/j.canlet.2006.03.027",

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AU - Werner, Haim

AU - Idelman, Gila

AU - Rubinstein, Moran

AU - Pattee, Patrick

AU - Nagalla, Srinivasa R.

AU - Roberts, Charles T.

N1 - Funding Information: These studies were supported by grants from the Israel Cancer Association to H.W., the US-Israel Binational Science Foundation (BSF) and the Fogarty International Center (FIRCA) to H.W. and C.T.R., Jr, and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, to C.T.R., Jr. S.R.N. and C.T.R., Jr., thank T.B. Moore, M.D., for referral of this patient and Scott Kuhn for expert technical assistance.

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N2 - Desmoplastic small round cell tumor (DSRCT) is a primitive sarcoma characterized by a recurrent chromosomal translocation, t(11;22)(p13;q12), which fuses the 5′ exons of the EWS gene to the 3′ exons of the WT1 gene. EWS-WT1 chimeras are heterogeneous as a result of fusions of different regions of the EWS gene to the WT1 gene. We report here a rare and novel EWS-WT1 variant, EWS-WT1 5/10, in a 6-year-old boy diagnosed with DSRCT and analyze the potential transactivation effect of the fusion oncoprotein. The predicted product is comprised of the N-terminal transactivation domain of EWS and lacks any sequence derived from the WT1 gene product. Nonetheless, the truncated protein was able to stimulate expression of the insulin-like growth factor-I receptor gene, a potent antiapoptotic receptor tyrosine kinase with potentially important roles in DSRCT etiology. These findings raise the possibility that the oncogenic potential of EWS-WT1 fusions is not necessarily a consequence of the fusion protein product per se.

AB - Desmoplastic small round cell tumor (DSRCT) is a primitive sarcoma characterized by a recurrent chromosomal translocation, t(11;22)(p13;q12), which fuses the 5′ exons of the EWS gene to the 3′ exons of the WT1 gene. EWS-WT1 chimeras are heterogeneous as a result of fusions of different regions of the EWS gene to the WT1 gene. We report here a rare and novel EWS-WT1 variant, EWS-WT1 5/10, in a 6-year-old boy diagnosed with DSRCT and analyze the potential transactivation effect of the fusion oncoprotein. The predicted product is comprised of the N-terminal transactivation domain of EWS and lacks any sequence derived from the WT1 gene product. Nonetheless, the truncated protein was able to stimulate expression of the insulin-like growth factor-I receptor gene, a potent antiapoptotic receptor tyrosine kinase with potentially important roles in DSRCT etiology. These findings raise the possibility that the oncogenic potential of EWS-WT1 fusions is not necessarily a consequence of the fusion protein product per se.

KW - DSRCT

KW - EWS-WT1

KW - IGF receptor

KW - Insulin-like growth factor-I

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A novel EWS-WT1 gene fusion product in desmoplastic small round cell tumor is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene

Abstract

Funding

Keywords

UN SDGs

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