Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 13, 2020
- Source ID
- 10.7554/elife.51480
Entities
People
- Alex Krasnitz
- Anthony Leotta
- Assaf Gordon
- Christina Curtis
- Frank Ambrosio
- Gouri Nanjangud
- Hilary Cox
- James Hicks
- Jie Wu
- Jude Kendall
- Junyan Song
- Kalyani Chadalavada
- Katherine Mcnamara
- Konstantin Volyanskyy
- Linda Rodgers
- Lyndsay Harris
- Michael Riggs
- Michael Wigler
- Nevenka Dimitrova
- Rodrigo Gularte-mérida
- Ronak Shah
- Sean D'italia
- Timour Baslan
- Vinay Varadan
- Yong Mao
Organizations
- American Cancer Society
- Case Western Reserve University
- Cold Spring Harbor Laboratory
- Memorial Sloan Kettering Cancer Center
- National Institutes of Health
- Stanford University
- Stony Brook University
- Susan G. Komen for the Cure
- The Breast Cancer Research Foundation
- United States Department of Defense