在结肠癌中出现反复的R-spondin融合
Somasekar Seshagiri1, Eric W Stawiski, Steffen Durinck
1Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. sekar@gene.com
Nature
|August 17, 2012
概括
研究人员在结肠癌基因中发现了新的复发性突变,包括Wnt通路和染色质重塑基因. 这些发现为结肠癌治疗提供了潜在的新治疗点.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 了解癌症的基因组变化对于开发向疗法至关重要.
- 结肠癌表现出复杂的遗传变化,导致瘤的进展.
研究的目的:
- 系统地分析外体,转录体和副本数量的变化在人类初级结肠瘤的队列.
- 在结肠癌中识别新的复发性突变和基因融合,以潜在的治疗向.
主要方法:
- 下一代测序 (NGS) 用于分析超过70对人类初级结肠瘤.
- 综合分析包括外基因组测序,转录基因组测序 (RNA-seq) 和副本数量改变概况.
主要成果:
- 鉴定了36303种蛋白质改变的体质变化,包括TCF7L2,TET2,TET3和ERBB3.3中的新复发突变.
- 发现了23个显著突变的癌症基因候选者,包括ATM. 确定了IGF2放大和过度表达.
- 在10%的瘤中发现了涉及RSPO2和RSPO3的复发性基因融合,这些基因融合增强了Wnt信号传递,并且与APC突变相互排斥.
结论:
- 该研究确定了结肠癌中的新型遗传变异,包括Wnt途径和染色质重塑基因突变以及RSPO基因融合.
- 这些发现为结肠癌瘤发生提供了新的见解,并突出了潜在的新治疗干预点.
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