Haplotype-resolved Assemblies of the MHC Region in Five Widely Used Tumor Cell Lines

This study addresses the challenges posed by the high polymorphism of the major histocompatibility complex (MHC) region. We developed high-quality, haplotype-resolved assemblies of the MHC region in five widely used tumor cell lines: A549, HeLa, HepG2, K562, and U2OS, which serve as key models for cancer research and drug development. By combining CRISPR-based targeted enrichment with 10x Genomics linked-read and PacBio HiFi long-read sequencing, we produced accurate MHC haplotypes for each cell line. These assemblies overcome the limitations of conventional reference genomes, enabling more reliable genetic and epigenetic analyses. Additionally, we characterized aneuploidy in the MHC region across these cell lines, providing valuable insights into the genetic landscape of this immunologically significant locus. This resource is expected to facilitate deeper understanding of tumor biology, immune responses, and the development of targeted therapies.