1. Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell genome sequencing.
- Author
-
Baslan T, Kendall J, Volyanskyy K, McNamara K, Cox H, D'Italia S, Ambrosio F, Riggs M, Rodgers L, Leotta A, Song J, Mao Y, Wu J, Shah R, Gularte-Mérida R, Chadalavada K, Nanjangud G, Varadan V, Gordon A, Curtis C, Krasnitz A, Dimitrova N, Harris L, Wigler M, and Hicks J
- Subjects
- Breast Neoplasms mortality, Breast Neoplasms pathology, Breast Neoplasms therapy, Clinical Trials, Phase II as Topic, Female, Genetic Predisposition to Disease, Humans, Phenotype, Prognosis, RNA-Seq, Biomarkers, Tumor genetics, Breast Neoplasms genetics, DNA Copy Number Variations, Gene Dosage, Genetic Heterogeneity, Genomics, Single-Cell Analysis, Whole Genome Sequencing
- Abstract
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., Competing Interests: TB, JK, KV, KM, HC, SD, FA, MR, LR, AL, JS, YM, RS, RG, KC, GN, VV, CC, AK, LH, MW, JH No competing interests declared, JW, ND is an employee of Philips Research North America. AG is affiliated with House Gordon Software Company LTD. The author has no other competing interests to declare.
- Published
- 2020
- Full Text
- View/download PDF