ETV6-NTRK3: a chimeric protein tyrosine kinase with transformation activity in multiple cell lineages

被引:106
作者
Lannon, CL
Sorensen, PHB [1 ]
机构
[1] BC Res Inst Childrens & Womens Hlth, Johal Program Pediat Oncol Basic & Translat Res, Dept Pathol, Vancouver, BC V5Z 4H4, Canada
[2] BC Res Inst Childrens & Womens Hlth, Dept Pediat, Vancouver, BC V5Z 4H4, Canada
[3] Univ British Columbia, Vancouver, BC V5Z 4H4, Canada
关键词
ETV6-NTRK3; translocation; chimeric tyrosine kinase; IRS-1; Tel;
D O I
10.1016/j.semcancer.2005.01.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The ETV6-NTRK3 (TEL-TRKC) gene fusion was discovered by breakpoint analysis of the t(12;15)(p13;q25) translocation associated with congenital fibrosarcoma, a pediatric soft tissue malignancy. ETV6-NTRK3 (EN) encodes the sterile alpha motif oligomerization domain of the ETV6 (TEL) transcription factor linked to the protein tyrosine kinase domain of the neurotrophin-3 receptor NTRK3 (TRKC). The EN chimeric oncoprotein links to multiple signaling cascades including Ras-MAP kinase and PI3K-AKT through the IRS-1 adapter protein. Recent evidence indicates that a functional insulin-like growth factor I receptor axis and higher order polymer formation are essential for EN oncogenesis. EN has been detected in other malignancies, including secretory breast carcinoma. This chimeric oncoprotein is therefore unique in being expressed in tumors derived from multiple cell lineages. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:215 / 223
页数:9
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