Novel Insights Into Breast Cancer Copy Number Genetic Heterogeneity Revealed by Single-Cell Genome Sequencing

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-Merida, R., Chadalavada, K., Nanjangud, G., Varadan, V., Gordon, A., Curtis, C., Krasnitz, A., Dimitrova, N., Harris, L., Wigler, M., Hicks, J. (May 2020) Novel Insights Into Breast Cancer Copy Number Genetic Heterogeneity Revealed by Single-Cell Genome Sequencing. Elife, 9. e51480. ISSN 2050-084X

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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.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders Investigative techniques and equipment diseases & disorders > neoplasms Investigative techniques and equipment > assays Investigative techniques and equipment > biomarker diseases & disorders > cancer > cancer types > breast cancer diseases & disorders > cancer > prognosis Investigative techniques and equipment > assays > RNA-seq diseases & disorders > cancer > cancer types
CSHL Authors:	Wigler, Michael H. Krasnitz, Alexander Baslan, Timour Kendall, Jude T. Cox, Hilary D'Italia, Sean Riggs, Michael Rodgers, Linda Leotta, Anthony Song, Junyan Hicks, James B. Ambrosio, Frank
Communities:	CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL labs > Krasnitz lab CSHL labs > Wigler lab CSHL Cancer Center Program
Depositing User:	Adrian Gomez
Date:	13 May 2020
Date Deposited:	01 Jun 2020 13:55
Last Modified:	13 Feb 2024 19:52
PMCID:	PMC7220379
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/39484

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