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同时存在的RET/PTC和TERT促进器突变预测预后不佳,但在甲状腺癌中有效的RET和MEK向
Wei Zhang1, Shuhuang Lin1, Zhuo Wang1
1Thyroid Research Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China.
The Journal of clinical endocrinology and metabolism
|May 12, 2024
概括
乳头甲状腺癌 (PTC) 与同时存在的RET/PTC和TERT促进子突变呈现出一种独特的,高死亡率的临床实体. 针对RET和MEK途径提供了基于遗传状态的潜在治疗策略.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 在乳头甲状腺癌 (PTC) 中RET/PTC重组的预后意义仍然不清楚.
- 了解基因变异对于改善PTC患者的治疗结果至关重要.
研究的目的:
- 研究在PTC中并存的RET/PTC重组和TERT促进子突变的预后和治疗影响.
- 探索这些基因变异在患者生存和治疗策略中的作用.
主要方法:
- 分析了669名PTC患者的临床和遗传数据,这些数据来自三个数据集 (TCGA-THCA,MSK-Metropism,MSK-IMPACT).
- 专注于163名野生型BRAF/RAS患者,进行基因型对死亡率的比较队列分析.
- 包括竞争指数和风险比率在内的统计分析,经人口统计因素调整.
主要成果:
- 观察到RET/PTC和TERT促进子突变之间存在显著的竞争 (P = .023).
- 患有两种突变的患者的死亡率明显高 (50%),相比于没有任何突变或单一突变的患者.
- RET/PTC通过MAP激酶通路调节突变的TERT,这表明RET和MEK是治疗点.
结论:
- 同时存在的RET/PTC和TERT促进子突变定义了一个独特的PTC亚型,预后不佳.
- 这一发现对PTC的基因预后有影响.
- 针对RET和MEK途径为具有特定遗传特征的患者提供了潜在的治疗途径.
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