Long-read sequencing of single cell-derived melanoma subclones reveals divergent and parallel genomic and epigenomic evolutionary trajectories.

ABSTRACT: Tumor evolution is driven by various mutational processes, ranging from single-nucleotide variants (SNVs) to large structural variants (SVs) to dynamic shifts in DNA methylation. Current short-read sequencing methods struggle to accurately capture the full spectrum of these genomic and epigenomic alterations due to inherent technical limitations. To overcome that, here we introduce an approach for long-read sequencing of single-cell derived subclones, and use it to profile 23 subclones of a mouse melanoma cell line, characterized with distinct growth phenotypes and treatment responses. We develop a computational framework for harmonization and joint analysis of different variant types in the evolutionary context. Uniquely, our framework enables detection of recurrent amplifications of puta

SUBMITTER: Liu Y 

PROVIDER: S-EPMC12424993 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature