Integrated analysis of extrachromosomal DNA elements in SCLC [HiChIP]

Integrated analysis of whole-genome sequencing, long-range optical mapping, single-cell DNA sequencing, and fluorescence in situ hybridization to find extrachromosomal DNA (ecDNA) as the primary source of MYC amplifications and driver fusions in SCLC. ecDNAs bring to proximity enhancer elements and oncogenes through circularization, creating transcription-amplifying units, driving heterogeneity of MYC gene dosage and expression of SCLC lineage-defining transcription factors. Overall design: H3K27ac HiChIP samples.

本研究整合全基因组测序（whole-genome sequencing）、长程光学作图（long-range optical mapping）、单细胞DNA测序（single-cell DNA sequencing）与荧光原位杂交（fluorescence in situ hybridization, FISH）技术，旨在鉴定染色体外DNA（extrachromosomal DNA, ecDNA）作为小细胞肺癌（Small Cell Lung Cancer, SCLC）中MYC基因扩增与驱动基因融合的主要来源。ecDNA通过环化作用使增强子元件与癌基因相互邻近，形成转录扩增单元，进而驱动MYC基因剂量异质性，并调控小细胞肺癌谱系特征性转录因子的表达。实验整体设计：H3K27ac HiChIP样本。