截断的FGFR2是一种在多种癌症中具有临床作用的瘤基因
Daniel Zingg1,2, Jinhyuk Bhin1,2,3, Julia Yemelyanenko1,2
1Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
截断的纤维细胞生长因子受体2 (FGFR2) 异位18的改变是强大的癌症驱动因素. 这些FGFR2变异代表了针对多种癌症的FGFR向治疗的可操作的治疗标.
科学领域:
- 癌症学
- 分子生物学
- 遗传学
背景情况:
- 纤维细胞生长因子受体2 (FGFR2) 改变,包括突变,放大和融合,与各种癌症有关.
- 对FGFR抑制剂的临床反应是可变的,突出显示需要确定特定的瘤性FGFR2变化.
研究的目的:
- 调查不同FGFR2变化的致癌潜力.
- 识别特定的FGFR2变异,这些变异是可以针对治疗的.
主要方法:
- 使用基于转子体的查和小鼠瘤建模.
- 用于检查FGFR2变异的功能性体外和体内测试.
- 分析了人类瘤基因组数据集.
主要成果:
- 鉴定出Fgfr2 (FGFR2ΔE18) 的第18个外显子 (E18) 是一个强大的驱动突变.
- 多种FGFR2变化,包括重组和无意义/移突变,导致FGFR2ΔE18.
- 截断FGFR2-E18作为单驱动器改变,而全长的FGFR2放大需要合作基因.
结论:
- 产生稳定的FGFR2ΔE18变异的基因组变化是可行的治疗点.
- 支持针对FGFR2ΔE18的临床前和临床数据.
- 任何FGFR2变异的癌症都应考虑针对FGFR的治疗.
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