Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell genome sequencing
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....
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/51480 |
| _version_ | 1818024097222754304 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Timour Baslan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T03:54:48Z |
| format | Article |
| id | doaj.art-b100cf9df74a4bccbe9405981826f8e4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:54:48Z |
| publishDate | 2020-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b100cf9df74a4bccbe9405981826f8e42022-12-22T02:03:09ZengeLife Sciences Publications LtdeLife2050-084X2020-05-01910.7554/eLife.51480Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell genome sequencingTimour Baslan0https://orcid.org/0000-0001-5674-6432Jude Kendall1Konstantin Volyanskyy2Katherine McNamara3Hilary Cox4Sean D'Italia5Frank Ambrosio6Michael Riggs7Linda Rodgers8Anthony Leotta9Junyan Song10Yong Mao11Jie Wu12Ronak Shah13Rodrigo Gularte-Mérida14Kalyani Chadalavada15Gouri Nanjangud16Vinay Varadan17https://orcid.org/0000-0003-1520-1967Assaf Gordon18Christina Curtis19Alex Krasnitz20Nevenka Dimitrova21Lyndsay Harris22Michael Wigler23James Hicks24Cold Spring Harbor Laboratory, Cold Spring Harbor, United States; Department of Molecular and Cellular Biology, Stony Brook University, Stony Brook, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesPhilips Research North America, Biomedical Informatics, Cambridge, United StatesDepartment of Genetics, Stanford University School of Medicine, Stanford, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United States; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, United StatesPhilips Research North America, Biomedical Informatics, Cambridge, United StatesPhilips Research North America, Biomedical Informatics, Cambridge, United StatesCenter for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, United StatesDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, United StatesMolecular Cytogenetics Core Facility, Memorial Sloan Kettering Cancer Center, New York, United StatesMolecular Cytogenetics Core Facility, Memorial Sloan Kettering Cancer Center, New York, United StatesCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United StatesHouse Gordon Software Company LTD, Calgary, CanadaDepartment of Genetics, Stanford University School of Medicine, Stanford, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesPhilips Research North America, Biomedical Informatics, Cambridge, United StatesCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States; Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, United States; Seidman Cancer Center, University Hospitals of Case Western, Cleveland, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesCopy 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.https://elifesciences.org/articles/51480cancergenomicssingle-cell sequencingcopy number alterationsgeneticsbreast cancer |
| spellingShingle | 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 Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell genome sequencing eLife cancer genomics single-cell sequencing copy number alterations genetics breast cancer |
| title | Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell genome sequencing |
| title_full | Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell genome sequencing |
| title_fullStr | Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell genome sequencing |
| title_full_unstemmed | Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell genome sequencing |
| title_short | Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell genome sequencing |
| title_sort | novel insights into breast cancer copy number genetic heterogeneity revealed by single cell genome sequencing |
| topic | cancer genomics single-cell sequencing copy number alterations genetics breast cancer |
| url | https://elifesciences.org/articles/51480 |
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