乳腺侵袭性叶状癌缺乏CDH1遗传改变的基因组和表观基因组基础
Higinio Dopeso1, Andrea M Gazzo1, Fatemeh Derakhshan1,2
1Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
NPJ precision oncology
|February 12, 2024
概括
乳腺侵袭性叶状癌 (ILC) 通常涉及CDH1的不活化. 这项研究发现,一些缺乏CDH1变化的ILCs是由其他细胞粘附基因的突变驱动的,如AXIN2和CTNND1,揭示了融合的表型.
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:
- 乳腺侵袭性叶状癌 (ILC) 的特征是CDH1 (E-cadherin) 的双基失活,从而导致一个异性细胞表型.
- 一部分ILC病例没有表现出CDH1遗传或表观遗传失活,潜在的遗传驱动因素在很大程度上仍然未知.
研究的目的:
- 调查在缺乏CDH1无活化的病例中驱动ILC的遗传变化.
- 为了确定ILC表型的其他遗传驱动因素.
主要方法:
- 从364个初级ILC样本中重新分析临床向测序数据.
- 在选定的缺乏CDH1变化的病例中进行了全基因组测序.
- 功能性研究涉及AXIN2在MCF7细胞中的淘汰.
主要成果:
- 确定了25个没有CDH1双基遗传变化的ILC;63%显示CDH1促进物甲基化.
- 在3个案例中发现了AXIN2中的有害突变或融合.
- 全基因组测序发现CTNND1 (p120) 有害的融合在一个没有CDH1无活化的情况下.
- 在MCF7细胞中,AXIN2的淘汰诱导了叶片状特征,包括增加的迁移和anoikis抗性.
结论:
- 缺乏CDH1遗传或表观遗传失活化的ILCs可以通过其他细胞粘附基因的失活变化,特别是CTNND1或AXIN2.2,来驱动.
- 这些替代遗传变化汇聚在一起,产生类似的异性ILC表型,突出显示ILC发展的替代途径.
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