Resolving clonal evolution and selection of extrachromosomal DNA at single-cell resolution.

ABSTRACT:

Background

Genomic alterations are a hallmark of cancer, and extrachromosomal DNA (ecDNA) has emerged as a key source of oncogene selection, tumor growth, and drug resistance. The intratumor heterogeneity and clonal selection of ecDNA is, however, poorly understood.

Results

In this study, we pursue a computational approach that leverages allelic imbalance and outlier expression from standard single-cell RNA sequencing (scRNA-seq) to deconvolve the tumor heterogeneity of ecDNA at the single-cell level (ecSingle). Using this approach, we identify oncogene-carrying ecDNAs in tumor samples at the single-cell level, which we validate using genome sequencing. Moreover, we show the superiority of using single-molecule long-read sequencing in resolving ecDNA. ecDNAs displayed extens

SUBMITTER: Hendriksen JD 

PROVIDER: S-EPMC12853921 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature