Temporal evolution of cellular heterogeneity during the progression to advanced, AR-negative prostate cancer [ChIP-seq]. Temporal evolution of cellular heterogeneity during the progression to advanced, AR-negative prostate cancer [ChIP-seq]

Despite advances in the development of highly effective androgen receptor (AR)-directed therapies for the treatment of men with advanced prostate cancer, acquired resistance ultimately ensues. A significant subset of patients with resistant disease develop AR-null, androgen-indifferent tumors that lose their luminal identify and display neuroendocrine features (neuroendocrine prostate cancer (NEPC)). Utilizing a genetically engineered mouse model, we have characterized the synergy between N-Myc overexpression and RB1 loss-of-function which results in the formation of AR-negative, poorly differentiated tumors with high metastatic potential. Single-cell-based approaches revealed striking changes to the transcriptome and chromatin accessibility during the transition to NEPC. Global DNA methylation and the N-Myc cistrome are redirected following RB1 loss. Altogether, our data provide new insight into the progression to NEPC. Overall design: N-Myc ChIP-seq in mouse prostate tumors Please note that each processed data was generated from both input and IP samples, and is linked to the corresponding IP sample records.

尽管针对晚期前列腺癌男性患者的高效雄激素受体（androgen receptor, AR）靶向治疗已取得诸多进展，但最终仍不可避免地会出现获得性耐药。存在相当比例的耐药患者会发展为AR阴性、雄激素非依赖性肿瘤，此类肿瘤丧失管腔表型，并呈现神经内分泌特征（神经内分泌前列腺癌（neuroendocrine prostate cancer, NEPC））。本研究借助基因工程小鼠模型，对N-Myc过表达与RB1功能缺失之间的协同效应进行了表征，二者协同可诱导形成具有高转移潜能的AR阴性低分化肿瘤。基于单细胞的分析方法揭示了向NEPC转化过程中，转录组与染色质可及性发生的显著改变。RB1缺失后，全基因组DNA甲基化模式及N-Myc结合位点组发生重编程。综上，本研究数据为神经内分泌前列腺癌的发生进展提供了全新的研究视角。整体实验设计：小鼠前列腺肿瘤中的N-Myc染色质免疫共沉淀测序（ChIP-seq）。请注意，所有处理后的数据均由输入样本与免疫沉淀（immunoprecipitation, IP）样本共同生成，并与对应的IP样本记录相关联。