Tumour evolution inferred by single-cell sequencing
Nicholas Navin,Jude Kendall,Jennifer Troge,Peter Andrews,Linda Rodgers,Jeanne McIndoo,Kerry Cook,Asya Stepansky,Dan Levy,Diane Esposito,Lakshmi Muthuswamy,Alexander Krasnitz,W. Richard McCombie,James W. Hicks,Michael Wigler +14 more
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TLDR
It is shown that with flow-sorted nuclei, whole genome amplification and next generation sequencing the authors can accurately quantify genomic copy number within an individual nucleus and indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.Abstract:
Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse 'pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.read more
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Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate
Mark M. Stevens,Cecile L. Maire,Nigel Chou,Mark A. Murakami,David S. Knoff,Yuki Kikuchi,Yuki Kikuchi,Robert J. Kimmerling,Huiyun Liu,Samer Haidar,Nicholas L. Calistri,Nathan Cermak,Selim Olcum,Nicolas A. Cordero,Ahmed Idbaih,Patrick Y. Wen,David M. Weinstock,David M. Weinstock,Keith L. Ligon,Scott R. Manalis +19 more
TL;DR: In this article, the single-cell mass accumulation rate (MAR) was used to predict drug response using samples as small as 25 μl of peripheral blood while maintaining cell viability and compatibility with downstream characterization.
Journal ArticleDOI
SNES: single nucleus exome sequencing
TL;DR: A method is developed that combines flow-sorting of single G1/0 or G2/M nuclei, time-limited multiple-displacement-amplification, exome capture, and next-generation sequencing to generate high coverage data from single human cells, resulting in high detection efficiencies for single nucleotide variants and indels in single cells.
Journal ArticleDOI
Tumour Cell Heterogeneity.
Ann-Marie Baker,Trevor A. Graham +1 more
TL;DR: The extent of intra-tumour heterogeneity (ITH) across human malignancies is summarized, the mechanisms that are responsible for generating and maintaining ITH are reviewed, and the ramifications and opportunities that ITH presents for cancer prognostication and treatment are discussed.
Journal ArticleDOI
Tumour heterogeneity and the evolutionary trade-offs of cancer
Jean Hausser,Uri Alon +1 more
TL;DR: The theory of multi-task evolution of cancer, which is based upon the premise that tumours evolve in the host and face selection trade-offs between multiple biological functions, is reviewed.
Journal ArticleDOI
A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast.
Bhupinder Pal,Yunshun Chen,Yunshun Chen,François Vaillant,François Vaillant,Bianca D. Capaldo,Bianca D. Capaldo,Rachel Joyce,Rachel Joyce,Xiaoyu Song,Xiaoyu Song,Vanessa L. Bryant,Vanessa L. Bryant,Jocelyn S Penington,Jocelyn S Penington,Leon Di Stefano,Leon Di Stefano,Nina Tubau Ribera,Stephen Wilcox,GB Mann,Anthony T. Papenfuss,Geoffrey J. Lindeman,Geoffrey J. Lindeman,Gordon K. Smyth,Jane E. Visvader,Jane E. Visvader +25 more
TL;DR: In this article, the authors examined global changes in breast heterogeneity across different states, determined the single-cell transcriptomes of > 340,000 cells encompassing normal breast, preneoplastic BRCA1+/- tissue, the major breast cancer subtypes, and pairs of tumors and involved lymph nodes.
References
More filters
Journal ArticleDOI
The neighbor-joining method: a new method for reconstructing phylogenetic trees.
Naruya Saitou,Masatoshi Nei +1 more
TL;DR: The neighbor-joining method and Sattath and Tversky's method are shown to be generally better than the other methods for reconstructing phylogenetic trees from evolutionary distance data.
Journal ArticleDOI
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome
TL;DR: Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches and can be used simultaneously to achieve even greater alignment speeds.
Journal ArticleDOI
The clonal evolution of tumor cell populations
TL;DR: Each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment, which should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.
Journal ArticleDOI
Distant metastasis occurs late during the genetic evolution of pancreatic cancer
Shinichi Yachida,Siân Jones,Ivana Bozic,Tibor Antal,Tibor Antal,Rebecca J. Leary,Baojin Fu,Mihoko Kamiyama,Ralph H. Hruban,James R. Eshleman,Martin A. Nowak,Victor E. Velculescu,Kenneth W. Kinzler,Bert Vogelstein,Christine A. Iacobuzio-Donahue +14 more
TL;DR: In this article, the authors rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers and find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone.
SF-010-4 Distant metastasis occurs late during the genetic evolution of pancreatic cancer
TL;DR: A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell.
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