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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Dissecting genomic diversity, one cell at a time
Paul C. Blainey,Stephen R. Quake +1 more
TL;DR: Emerging technologies are bringing single-cell genome sequencing into the mainstream and have already yielded insights into the genetic architecture and variability between cells that highlight the dynamic nature of the genome.
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Breast Cancer Genomics From Microarrays to Massively Parallel Sequencing: Paradigms and New Insights
Charlotte K.Y. Ng,Anne M. Schultheis,François-Clément Bidard,Britta Weigelt,Jorge S. Reis-Filho +4 more
TL;DR: Harnessing the emerging concepts of the diversity of breast cancer genomes and the phenomenon of intratumor genetic heterogeneity will be essential for the development of optimal methods for diagnosis, disease monitoring, and the matching of patients to the drugs that would benefit them the most.
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Genomic Profiling Defines Subtypes of Prostate Cancer with the Potential for Therapeutic Stratification
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The Case for a Pre-Cancer Genome Atlas (PCGA)
Joshua D. Campbell,Sarah A. Mazzilli,Mary E. Reid,Samjot Singh Dhillon,Suso Platero,Jennifer Beane,Avrum Spira +6 more
TL;DR: Genomic characterization of alterations in premalignant lesions and their microenvironment will enable development of biomarkers for early detection and risk stratification as well as allow for the development of novel targeted cancer interception strategies.
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Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.
Foad J. Rouhani,Foad J. Rouhani,Serena Nik-Zainal,Arthur Wuster,Yang Li,Nathalie Conte,Hiroko Koike-Yusa,Natsuhiko Kumasaka,Ludovic Vallier,Ludovic Vallier,Kosuke Yusa,Allan Bradley +11 more
TL;DR: By sequencing the genomes of polyclonal and monoclonal somatic cells and derived iPSCs, the mutation rates are determined and how the patterns change from a somatic lineage in vivo through toiPSCs are shown.
References
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