Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell genome sequencing
2020
Timour Baslan | Jude Kendall | Konstantin Volyanskyy | Katherine McNamara | Hilary Cox | Sean D'Italia | Frank Ambrosio | Michael Riggs | Linda Rodgers | Anthony Leotta | Junyan Song | Yong Mao | Jie Wu | Ronak Shah | Rodrigo Gularte-Mérida | Kalyani Chadalavada | Gouri Nanjangud | Vinay Varadan | Assaf Gordon | Christina Curtis | Alex Krasnitz | Nevenka Dimitrova | Lyndsay Harris | Michael Wigler | James Hicks
Copy number alterations (CNAs) play an important role in molding the genomes of breast cancers and have been shown to be clinically useful for prognostic and therapeutic purposes. However, our knowledge of intra-tumoral genetic heterogeneity of this important class of somatic alterations is limited. Here, using single-cell sequencing, we comprehensively map out the facets of copy number alteration heterogeneity in a cohort of breast cancer tumors. Ou/var/www/html/elife/12-05-2020/backup/r analyses reveal: genetic heterogeneity of non-tumor cells (i.e. stroma) within the tumor mass; the extent to which copy number heterogeneity impacts breast cancer genomes and the importance of both the genomic location and dosage of sub-clonal events; the pervasive nature of genetic heterogeneity of chromosomal amplifications; and the association of copy number heterogeneity with clinical and biological parameters such as polyploidy and estrogen receptor negative status. Our data highlight the power of single-cell genomics in dissecting, in its many forms, intra-tumoral genetic heterogeneity of CNAs, the magnitude with which CNA heterogeneity affects the genomes of breast cancers, and the potential importance of CNA heterogeneity in phenomena such as therapeutic resistance and disease relapse.
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