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晚期前列腺癌中可访问的染色质图谱揭示了瘤进展期间的表观遗传进化

Raunak Shrestha^1,2, Lisa N Chesner^1,2, Meng Zhang^1,2

¹Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.

Cancer research

|July 11, 2024

概括

晚期前列腺癌 (mCRPC) 通过表观遗传变化发展抵抗力. 这项研究绘制了染色质可访问性的地图,确定ZNF263是治疗耐药亚型中的关键转录因子.

科学领域:

表观遗传学和癌症生物学
基因组学和分子瘤学

背景情况:

转移性割抵抗性前列腺癌 (mCRPC) 是一种由雄激素信号驱动的致命恶性瘤.
mCRPC通过雄激素受体 (AR) 信号放大或AR独立亚型发展治疗耐药性.
了解mCRPC亚型的表观遗传基础对于识别耐药机制至关重要.

研究的目的:

在mCRPC中描述全球色素可访问性概况.
为了确定与mCRPC亚型相关的谱系特异性转录因子 (TF).
为了阐明晚期前列腺癌中疗法耐药性的表观遗传基础.

主要方法:

在70个mCRPC组织活检上使用转化酶可访问染色体测序 (ATAC-seq) 的测试进行染色体可访问性映射.
ATAC-seq数据与转录组和全基因组测序的整合.
在可访问的染色体区域中分析转录因子占用率.

主要成果:

mCRPC表现出与AR功能相关的独特的全球色素可访问性概况.
鉴定出203种转录因子与mCRPC亚型有显著关联.
鉴定ZNF263为假定前列腺癌TF,影响AR阴性,神经内分泌亚型的基因活性,并可能激活MYC标.

结论:

这项研究提供了晚期前列腺癌中染色质可访问性变化的全面描述.
鉴定亚型特异性TF提供了对mCRPC治疗耐药性的表观遗传驱动因素的见解.
在特定的mCRPC亚型中,ZNF263成为潜在的治疗标.

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