在正常前列腺,良性前列腺增生和同时存在的前列腺癌中体质突变的空间结构
Jeesoo Chae1,2, Seung-Hyun Jung3,4,5, Eun Ji Choi6
1Department of Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, 06591, Seoul, South Korea.
Experimental & molecular medicine
|January 3, 2024
概括
良性前列腺增生 (BPH) 与正常前列腺组织有一些基因组相似之处,与前列腺癌 (PCA) 有显著差异. 这表明BPH与衰老和环境因素比癌症发展更相关.
科学领域:
- 生殖尿路病理学
- 癌症基因组学 癌症基因组学
- 分子生物学分子生物学
背景情况:
- 在正常前列腺和良性前列腺增生 (BPH) 组织中,非瘤源的体性突变 (NSM) 尚不清楚.
- BPH和前列腺癌 (PCA) 之间的基因组关系尚不清楚.
研究的目的:
- 在正常的前列腺和BPH组织中识别NSM.
- 将BPH的基因组景观与正常的前列腺和PCA进行比较.
- 为了确定BPH和PCA发展之间的潜在关系.
主要方法:
- 来自22名患者的正常,BPH和PCA样本的全基因组测序.
- 前列腺组织的3D映射和三重采样.
- 对体突变,拷贝数变化 (CNA) 和结构变异的分析.
主要成果:
- 正常和BPH组织含有驱动性NSM和CNA (例如,在FOXA1),但其发病率较低,很少与PCA重叠.
- 比正常组织更高的突变负担,更短的端粒,更大的克隆大小和更多的私有NSM.
- BPH的基因组概况与正常前列腺不同,但比PCA更接近正常,表明BPH的瘤性较小.
结论:
- BPH基因组不同于正常的前列腺,但没有直接的致癌途径到PCA.
- 比起癌症的进展,BPH的发展可能更多地与衰老或环境暴露有关.
- 非癌性组织中的NSM提供了对早期基因组事件和组织稳态的洞察.
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