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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Stereotactic Body Radiotherapy for Oligometastasis: Opportunities for Biology to Guide Clinical Management.
TL;DR: Oligometastasis refers to a state of limited metastatic disease burden, in which surgical or ablative treatment to all known visible metastases holds promise to extend survival or even effect cure, and a lack of clear identification criteria or biomarkers to define the oligometastatic state hampers optimal patient selection.
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Molecular methods for genotyping complex copy number polymorphisms.
TL;DR: The basis of a number of molecular techniques used to genotype complex CNPs are described, compare and contrast these approaches for determination of multi-allelic copy number, and the potential application of these techniques in genetic studies is discussed.
Journal ArticleDOI
Precision Oncology Decision Support: Current Approaches and Strategies for the Future.
Katherine C. Kurnit,Ecaterina Ileana Dumbrava,Beate C. Litzenburger,Yekaterina B. Khotskaya,Amber Johnson,Timothy A. Yap,Jordi Rodon,Jia Zeng,Abu Shufean,Ann Marie Bailey,Nora S. Sanchez,Vijaykumar Holla,John Mendelsohn,Kenna R. Mills Shaw,Elmer V. Bernstam,Gordon B. Mills,Funda Meric-Bernstam +16 more
TL;DR: This review outlines existing tools available for health care providers and precision oncology teams and highlights strategies for optimizing decision support and specific attention is given to the assays currently available for molecular testing, as well as considerations for interpreting alteration information.
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Regenerative NanoOctopus Based on Multivalent-Aptamer-Functionalized Magnetic Microparticles for Effective Cell Capture in Whole Blood.
Yongli Chen,Deependra Tyagi,Mingsheng Lyu,Andrew J. Carrier,Collins Nganou,Brian Youden,Wei Wang,Shufen Cui,Mark R. Servos,Ken D. Oakes,Shengnan He,Xu Zhang +11 more
TL;DR: Mimicking the features of octopuses, a device termed a "NanoOctopus" was developed for cancer cell isolation in whole blood that consists of long multimerized aptamer DNA strands, or tentacle DNA, immobilized on magnetic microparticle surfaces.
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Difference Makers: Chromosomal Instability versus Aneuploidy in Cancer.
TL;DR: Differences between aneuploidy and CIN are discussed and scenarios in which distinguishing them can be clinically relevant are described.
References
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