恶性PEComa中端粒的替代延长:与分子特征的相关性,包括ATRX基因突变状态
Ruihe Lin1, John M Gross1, Deyin Xing1
1Department of Pathology, Johns Hopkins Hospital, Baltimore MD.
概括
恶性PEComa经常表现出替代延长端粒 (ALT) 现型,这是ATRX变化强烈预测的. 一些恶性PEComa通过ATRX独立的机制激活ALT.
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:
- 恶性周脉上皮质细胞瘤 (PEComas) 携带转移的高风险.
- 关于恶性PEComa的遗传基础的数据有限.
- 在各种癌症中,ATRX突变与替代延长端粒 (ALT) 现型有关.
研究的目的:
- 调查ALT表型在恶性PEComa中的流行率.
- 为了将ALT表型与基因组变异相关联,特别是ATRX突变.
- 探索在PEComa中ALT激活的潜在ATRX独立机制.
主要方法:
- 免疫组织化学 (IHC) 用于ATRX蛋白表达.
- 下一代测序 (NGS) 用于基因改变 (TSC/mTOR通路,TFE3融合,ATRX).
- 端粒特异性光在位杂交 (FISH) 检测ALT表型.
主要成果:
- 52%的恶性PEComa具有TSC/mTOR通路突变或TFE3转位.
- 在32%的病例中,出现了反复的ATRX变异.
- 75%的分析的恶性PEComa通过FISH显示了ALT表型.
- 在75%的ALT阳性瘤中存在ATRX变异;100%的ATRX突变瘤是ALT阳性.
- 50%没有ATRX变化的瘤显示ALT,这表明在某些情况下ATRX独立激活.
结论:
- 在恶性PEComa中,ATRX变化是ALT表型的强有力的预测因素.
- 恶性PEComa的一个子集通过独立于已知的ATRX改变的机制激活ALT.
- 这项研究确定了ALT和恶性PEComa中的基因组特征之间的联系,扩大了这些罕见瘤中端粒维护的知识.
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