头部和部肠类腺癌:通过全转录组和外体组分析剖析致癌基因变异
Diana Bell1, Achim H Bell2, Randal S Weber3
1Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte, California.
概括
头部和部的肠类腺癌 (ITAC) 通常是由MLL3基因突变驱动的. 这些突变破坏了表观遗传调节,影响了这些罕见癌症中的细胞信号传递和增殖.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 鼻腔/鼻鼻的肠类腺癌 (ITAC) 是一种罕见但显著的头瘤.
- 这些ITAC的分子基础在很大程度上是未知的,因为它们的稀有性.
研究的目的:
- 为了研究头部和部ITACs的分子概况.
- 确定潜在的致癌驱动因素,并了解ITAC异质性的表观遗传基础.
主要方法:
- 整个转录基因组和整个外基因组的枪枪测序在21个头部和部腺癌 (10个鼻,11个鼻外腺癌) 上进行.
- 瘤和正常的粘膜样本从固定在甲上,嵌入氨酸的组织中进行微切割.
- 进行了差异基因表达分析和突变分析.
主要成果:
- 分析显示,鼻ITACs和外鼻ITACs之间存在不同的基因表达特征.
- 在所有研究的腺癌中,MLL3 (KMT2C) 基因中的功能丧失突变是最常见的发现.
- MLL3突变与染色质甲基化和重塑受损有关,影响多个瘤性途径.
结论:
- 头部和部ITACs经常是由MLL3功能丧失突变驱动的,导致表观遗传失调.
- 这些表观遗传变化会影响关键的细胞过程,包括信号传递,增殖和免疫反应,从而导致瘤异质.
- 这些发现为ITACs的分子病因和呼吸道粘膜中的细胞平衡提供了洞察力.
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