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同突变和遗传变异对RAS阳性不确定的甲状腺结节的恶性瘤风险的影响:一个机构经验
Lawrence Q Wong1, Zubair W Baloch2
1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 6 Founders Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
Endocrine pathology
|March 5, 2026
概括
甲状腺结核中的RAS突变很常见,但它们的预后作用尚不清楚. 与RAS突变同时发生的基因变异显著增加恶性瘤的风险,与孤立的RAS突变不同,突出了全面分子分析的必要性.
科学领域:
- 内分泌学 在内分泌学.
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 在甲状腺结节中经常检测到RAS原基因 (NRAS,HRAS,KRAS) 突变.
- 拉斯突变的预后意义,特别是与其他遗传变异结合,仍然不完全理解.
- 准确的甲状腺结节风险分层对于适当的患者管理至关重要.
研究的目的:
- 调查孤立的RAS突变与与甲状腺结节中同时发生的遗传变化相比RAS突变的临床和病理影响.
- 确定特定分子形状与恶性瘤风险之间的关联.
- 评估同时发生的突变对瘤攻击性的影响.
主要方法:
- 从2018年至2023年期间诊断的346名患者的354个甲状腺结节的回顾性分析.
- 进行全面的分子分析,以识别RAS突变和同时发生的遗传改变 (例如,EIF1AX,TERT).
- 分子发现与临床数据,病理诊断和手术后续结果的相关性.
主要成果:
- 在41.0%的结节中发现了孤立的RAS突变,而54.8%的RAS具有额外的改变;NRAS是最常见的RAS亚型.
- 恶性病发病率总体为52.3%,在64.6%的恶性病例中出现NRAS突变.
- 与单独的RAS突变 (p=0.0026) 相比,具有RAS突变加上同时发生的变化的结节显示出明显更高的恶性瘤风险 (54.3%具有一个额外的变化,近100%具有三个) .
- 孤立的RAS突变更频繁地与良性或惰性瘤相关,而同时发生的突变表明更具侵略性的表型.
结论:
- 与RAS突变同时发生的基因变异大大增加了甲状腺结节恶性瘤的风险,并与侵袭性瘤表型有关.
- 孤立的RAS突变更常见于惰性瘤中.
- 全面的分子分析对于精确的风险分层和指导不确定性甲状腺结节的管理至关重要.
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