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一个集成的临床基因组和转录基因组分组的中央冠状腺癌
Debora M Meijer1, Sanne Venneker2, Baptiste Ameline3
1Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands; Leiden Center for Computational Oncology, Leiden University Medical Center, Leiden, The Netherlands.
概括
这项研究揭示了超出IDH突变状态的,在冠状腺癌内不同的生物子组. 整合临床,基因组和基因表达数据,为潜在的治疗分层提供了对这种骨肉瘤的更细致的理解.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 中央常规性软骨肉瘤是第二个最常见的骨肉瘤,其组织学等级预测生存率.
- 异酸脱酶1 (IDH1) 和IDH2基因的突变会产生影响DNA甲基化和细胞分化的甲基代谢物.
- 目前仅基于IDH状态的分类是不够的,因为不同的DNA甲基化概况和潜在的子组.
研究的目的:
- 用综合的临床,IDH突变,基因表达和异构性丧失 (LOH) 数据来识别116种冠状腺癌中的生物亚组.
- 探索IDH突变型和IDH野生型冠状腺癌之间的临床关联和基因组差异.
- 为了进一步识别子组,调查转录组特征.
主要方法:
- 综合分析临床数据,IDH突变状态,RNA测序和全基因组LOH在116个冠状腺癌样本中.
- 在IDH野生型和IDH突变型瘤之间对LOH程度的比较分析.
- 用差异化标记物对RNA表达数据进行聚类,以识别转录组子组.
主要成果:
- 在性别,组织学等级,瘤部位和IDH突变状态之间发现了临床关联.
- RNA测序和LOH证实了IDH野生型和IDH突变瘤之间的区别,野生型的LOH更高.
- 转录形状分析确定了具有原体,骨质,静止状细胞或非分化形状的子组,每个都有特定的临床表现.
结论:
- 仅仅根据IDH状态对冠状腺癌的分类是一种过度简单化.
- 综合分析揭示了复杂的临床,基因组和转录基因组模式.
- 已识别的子组表明不同的前体细胞,并可能指导未来的治疗分层为冠状骨肉瘤.
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