在神经内分泌瘤中,CREBBP突变是负性SSTR2 PET的罪祸首
Arvin Haj-Mirzaian1,2, Shadi A Esfahani1,2, Umar Mahmood1,2
1Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Molecular imaging and biology
|August 8, 2025
概括
具有CREBBP突变的神经内分泌瘤 (NET) 患者的Ga-DOTATATE PET扫描结果呈阴性,生存率降低. 这些突变可能会影响体静止素受体2 (SSTR2) 表达,影响成像和治疗适宜性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 核医学是一种核医学.
背景情况:
- 神经内分泌瘤 (NETs) 是一种异质的瘤群.
- 68Ga-DOTATATE PET成像是NET的标准诊断工具,其向的是体静止素受体 (SSTR).
- 阴性Ga-DOTATATE PET扫描可能发生,需要对潜在的分子机制进行调查.
研究的目的:
- 在NET中识别与负的Ga-DOTATATE PET成像相关的分子和遗传因素.
- 探索遗传突变与NET中的SSTR2表达之间的关系.
- 整合整个外因子测序 (WES) 和单细胞RNA测序 (scRNA-seq) 数据.
主要方法:
- 对18名NET患者进行了68次Ga-DOTATATE和18次F-FDG PET/CT扫描后期分析.
- 循环瘤细胞的整体外体序列测序 (WES) 来自带有阴性PET扫描的患者.
- 单细胞RNA测序 (scRNA-seq) 和变异调用以根据SSTR2表达水平比较突变负担和遗传特征.
主要成果:
- 负68的Ga-DOTATATE扫描与生存率降低相关,无论瘤的等级如何.
- 负PET扫描的患者中,CREBBP突变很普遍 (67%),与对照组 (0%) 不一样.
- 观察到SSTR2突变 (33%) 和低/负SSTR2表达的细胞中较高的突变负担;CREBBP突变在约35%的NET细胞中被发现,并且经常与低SSTR2表达有关.
结论:
- 在NET中,CREBBP突变可能会降低SSTR2的表达.
- 具有突变CREBBP基因型的患者可能不会从SSTR2向的PET成像或放射性核酸治疗中受益.
- 基因分析,包括CREBBP突变状态,可以完善患者选择NET诊断和治疗方法.
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