Phased Whole-Genome Detection and Analysis of Structural Variants of Invasive Ductal and Lobular Breast Cancer Cell Lines

Abstract

Heterogeneity in estrogen receptor positive breast cancers is poorly understood. Copy number alterations and structural differences contribute to carcinogenesis. Current cell line genomes representing the histological subtypes, invasive ductal and invasive lobular carcinoma, are highly rearranged as well as underreported. Although the functional genomic characteristics of ductal cell lines are extensively studied and documented, the genomic sequences of lobular cell lines have not been greatly studied. Furthermore, any higher-order structural features have never been comprehensively characterized in both ductal and lobular cell lines. New sequencing technology, 10x synthetic long reads, offers improved resolution and identification of structural variant changes. We applied this technology to lobular and ductal cell lines to identify differences. Phased sequencing revealed that structural variants in cancer cell lines are diverse. These results contribute to the understanding of ER+ breast cancer by characterizing the genomic landscape. This comprehensive whole-genome analysis serves as a resource for future studies that utilize these cell lines. It is also an example for advanced, integrated whole-genome sequence and structure analysis of human genomes in general and in particular of cancer genomes with large numbers of complex structural variants.